Carrel name: keyword-compound-cord Creating study carrel named keyword-compound-cord Initializing database file: cache/cord-000445-2x7dfl1q.json key: cord-000445-2x7dfl1q authors: Paliwal, Sarvesh K.; Verma, Ankita Narayan; Paliwal, Shailendra title: Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances date: 2011-05-10 journal: Sci Pharm DOI: 10.3797/scipharm.1012-08 sha: doc_id: 445 cord_uid: 2x7dfl1q file: cache/cord-002237-200ondzx.json key: cord-002237-200ondzx authors: Dashtdar, Mehrab; Dashtdar, Mohammad Reza; Dashtdar, Babak; Khan, Gazala Afreen; Kardi, Karima title: Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than Cloxacillin Against Pseudomonas Aeruginosa date: 2016-09-17 journal: J Pharmacopuncture DOI: 10.3831/kpi.2016.19.026 sha: doc_id: 2237 cord_uid: 200ondzx file: cache/cord-003341-z5w56zeq.json key: cord-003341-z5w56zeq authors: Nguyen, Thi Thanh Hanh; Lee, Sun; Wang, Hsi-Kai; Chen, Hsin-Yen; Wu, Ying-Ta; Lin, Simon C.; Kim, Do-Won; Kim, Doman title: In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4 date: 2013-12-13 journal: Molecules DOI: 10.3390/molecules181215600 sha: doc_id: 3341 cord_uid: z5w56zeq file: cache/cord-003427-0dddrh4e.json key: cord-003427-0dddrh4e authors: El-Faham, Ayman; Farooq, Muhammad; Khattab, Sherine N.; Abutaha, Nael; Wadaan, Mohammad A.; Ghabbour, Hazem A.; Fun, Hoong-Kun title: Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives date: 2015-08-13 journal: Molecules DOI: 10.3390/molecules200814638 sha: doc_id: 3427 cord_uid: 0dddrh4e file: cache/cord-003539-tazd6dvm.json key: cord-003539-tazd6dvm authors: Yang, Kun; Jin, Ming-Ji; Quan, Zhe-Shan; Piao, Hu-Ri title: Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration date: 2019-03-02 journal: Molecules DOI: 10.3390/molecules24050884 sha: doc_id: 3539 cord_uid: tazd6dvm file: cache/cord-006139-9063uhox.json key: cord-006139-9063uhox authors: Egan, Timothy J; Kuter, David title: Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter date: 2013-03-27 journal: Future Microbiol DOI: 10.2217/fmb.13.18 sha: doc_id: 6139 cord_uid: 9063uhox file: cache/cord-011251-rjyipcfv.json key: cord-011251-rjyipcfv authors: Chernyshov, Vladimir V.; Yarovaya, Olga I.; Fadeev, Dmitry S.; Gatilov, Yuriy V.; Esaulkova, Yana L.; Muryleva, Anna S.; Sinegubova, Katherina O.; Zarubaev, Vladimir V.; Salakhutdinov, Nariman F. title: Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity date: 2019-02-28 journal: Mol Divers DOI: 10.1007/s11030-019-09932-9 sha: doc_id: 11251 cord_uid: rjyipcfv file: cache/cord-012773-wtgk2d68.json key: cord-012773-wtgk2d68 authors: Xu, Ming-ming; Ryan, Philip; Rudrawar, Santosh; Quinn, Ronald J; Zhang, Hai-yan; Mellick, George D title: Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein date: 2019-10-04 journal: Acta Pharmacol Sin DOI: 10.1038/s41401-019-0304-y sha: doc_id: 12773 cord_uid: wtgk2d68 file: cache/cord-013387-q91052qw.json key: cord-013387-q91052qw authors: Leão, Rozires P.; Cruz, Josiane V.; da Costa, Glauber V.; Cruz, Jorddy N.; Ferreira, Elenilze F. B.; Silva, Raí C.; de Lima, Lúcio R.; Borges, Rosivaldo S.; dos Santos, Gabriela B.; Santos, Cleydson B. R. title: Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach date: 2020-08-26 journal: Pharmaceuticals (Basel) DOI: 10.3390/ph13090209 sha: doc_id: 13387 cord_uid: q91052qw file: cache/cord-014863-jyti99xq.json key: cord-014863-jyti99xq authors: Karaküçük-İyidoğan, A.; Aydınöz, B.; Taşkın-Tok, T.; Oruç-Emre, E. E.; Balzarini, J. title: Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents date: 2019-05-15 journal: Pharm Chem J DOI: 10.1007/s11094-019-01968-3 sha: doc_id: 14863 cord_uid: jyti99xq file: cache/cord-016425-8yd2bkf1.json key: cord-016425-8yd2bkf1 authors: Strobel, Gary; Daisy, Bryn; Castillo, Uvidelio title: Novel Natural Products From Rainforest Endophytes date: 2005 journal: Natural Products DOI: 10.1007/978-1-59259-976-9_15 sha: doc_id: 16425 cord_uid: 8yd2bkf1 file: cache/cord-017041-0zxoq68m.json key: cord-017041-0zxoq68m authors: Volochnyuk, Dmitriy M.; Grygorenko, Oleksandr O.; Gorlova, Alina O. title: Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry date: 2014-06-13 journal: Fluorine in Heterocyclic Chemistry Volume 2 DOI: 10.1007/978-3-319-04435-4_7 sha: doc_id: 17041 cord_uid: 0zxoq68m file: cache/cord-000536-0mn1gbll.json key: cord-000536-0mn1gbll authors: Hu, Le-Le; Chen, Chen; Huang, Tao; Cai, Yu-Dong; Chou, Kuo-Chen title: Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date: 2011-12-29 journal: PLoS One DOI: 10.1371/journal.pone.0029491 sha: doc_id: 536 cord_uid: 0mn1gbll file: cache/cord-020010-q58x6xb0.json key: cord-020010-q58x6xb0 authors: nan title: 19th ICAR Abstracts: date: 2006-03-13 journal: Antiviral Res DOI: 10.1016/j.antiviral.2006.02.001 sha: doc_id: 20010 cord_uid: q58x6xb0 file: cache/cord-021013-xvc791wx.json key: cord-021013-xvc791wx authors: Wink, Michael title: Chapter 1 Allelochemical Properties or the Raison D'être of Alkaloids date: 2008-05-30 journal: nan DOI: 10.1016/s0099-9598(08)60134-0 sha: doc_id: 21013 cord_uid: xvc791wx file: cache/cord-021419-nypnib0h.json key: cord-021419-nypnib0h authors: Olsufyeva, Evgenia N.; Yankovskaya, Valentina S. title: Main trends in the design of semi-synthetic antibiotics of a new generation date: 2020-03-17 journal: nan DOI: 10.1070/rcr4892 sha: doc_id: 21419 cord_uid: nypnib0h file: cache/cord-023284-i0ecxgus.json key: cord-023284-i0ecxgus authors: nan title: Abstracts of publications related to QASR date: 2006-09-19 journal: nan DOI: 10.1002/qsar.19900090309 sha: doc_id: 23284 cord_uid: i0ecxgus file: cache/cord-023584-yaxawqhj.json key: cord-023584-yaxawqhj authors: Bucknall, R.A. title: The Continuing Search for Antiviral Drugs date: 2008-04-10 journal: Adv Pharmacol DOI: 10.1016/s1054-3589(08)60460-3 sha: doc_id: 23584 cord_uid: yaxawqhj file: cache/cord-024652-4i6kktl0.json key: cord-024652-4i6kktl0 authors: Santra, Hiran Kanti; Banerjee, Debdulal title: Natural Products as Fungicide and Their Role in Crop Protection date: 2020-05-12 journal: Natural Bioactive Products in Sustainable Agriculture DOI: 10.1007/978-981-15-3024-1_9 sha: doc_id: 24652 cord_uid: 4i6kktl0 file: cache/cord-025119-201ac32t.json key: cord-025119-201ac32t authors: Salman, Saad; Shah, Fahad H; Idrees, Jawaria; Idrees, Fariha; Velagala, Shreya; Ali, Johar; Khan, Abid A title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 journal: nan DOI: 10.2217/fvl-2020-0079 sha: doc_id: 25119 cord_uid: 201ac32t file: cache/cord-033493-kslzdy8q.json key: cord-033493-kslzdy8q authors: Hebishy, Ali M. S.; Salama, Hagar T.; Elgemeie, Galal H. title: New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity date: 2020-09-21 journal: ACS Omega DOI: 10.1021/acsomega.0c02675 sha: doc_id: 33493 cord_uid: kslzdy8q file: cache/cord-034363-6uscua0y.json key: cord-034363-6uscua0y authors: Cerda-Cavieres, Christopher; Quiroz, Gabriel; Iturriaga-Vásquez, Patricio; Rodríguez-Lavado, Julio; Alarcón-Espósito, Jazmín; Saitz, Claudio; Pessoa-Mahana, Carlos D.; Chung, Hery; Araya-Maturana, Ramiro; Mella-Raipán, Jaime; Cabezas, David; Ojeda-Gómez, Claudia; Reyes-Parada, Miguel; Pessoa-Mahana, Hernán title: Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands date: 2020-10-10 journal: Molecules DOI: 10.3390/molecules25204614 sha: doc_id: 34363 cord_uid: 6uscua0y file: cache/cord-103271-l9n27ocf.json key: cord-103271-l9n27ocf authors: Carozza, Jacqueline A; Brown, Jenifer A.; Böhnert, Volker; Fernandez, Daniel; AlSaif, Yasmeen; Mardjuki, Rachel E.; Smith, Mark; Li, Lingyin title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 journal: bioRxiv DOI: 10.1101/2020.05.30.125534 sha: doc_id: 103271 cord_uid: l9n27ocf file: cache/cord-252108-04xr5xdl.json key: cord-252108-04xr5xdl authors: Havrylyuk, Dmytro; Zimenkovsky, Borys; Vasylenko, Olexandr; Day, Craig W.; Smee, Donald F.; Grellier, Philippe; Lesyk, Roman title: Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones date: 2013-06-06 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2013.05.044 sha: doc_id: 252108 cord_uid: 04xr5xdl file: cache/cord-253276-mqcwk2ow.json key: cord-253276-mqcwk2ow authors: Desai, N. C.; Bhatt, Nayan; Somani, Hardik; Trivedi, Amit title: Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles date: 2013-09-30 journal: European Journal of Medicinal Chemistry DOI: 10.1016/j.ejmech.2013.06.029 sha: doc_id: 253276 cord_uid: mqcwk2ow file: cache/cord-254036-0karwgz2.json key: cord-254036-0karwgz2 authors: Wang, Runming; Li, Hongyan; Sun, Hongzhe title: Bismuth: Environmental Pollution and Health Effects date: 2019-09-12 journal: Encyclopedia of Environmental Health DOI: 10.1016/b978-0-12-409548-9.11870-6 sha: doc_id: 254036 cord_uid: 0karwgz2 file: cache/cord-255862-84u3c33m.json key: cord-255862-84u3c33m authors: Kim, Ji Won; Ha, Thi-Kim-Quy; Cho, Hyomoon; Kim, Eunhee; Shim, Sang Hee; Yang, Jun-Li; Oh, Won Keun title: Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut) date: 2017-07-01 journal: Bioorganic & Medicinal Chemistry Letters DOI: 10.1016/j.bmcl.2017.05.022 sha: doc_id: 255862 cord_uid: 84u3c33m file: cache/cord-259744-r9j5yzfc.json key: cord-259744-r9j5yzfc authors: McDonagh, Phillip; Sheehy, Paul A; Norris, Jacqueline M title: Identification and characterisation of small molecule inhibitors of feline coronavirus replication date: 2014-12-05 journal: Vet Microbiol DOI: 10.1016/j.vetmic.2014.10.030 sha: doc_id: 259744 cord_uid: r9j5yzfc file: cache/cord-260014-q5sug7uu.json key: cord-260014-q5sug7uu authors: Szűcs, Zsolt; Naesens, Lieve; Stevaert, Annelies; Ostorházi, Eszter; Batta, Gyula; Herczegh, Pál; Borbás, Anikó title: Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity date: 2020-06-29 journal: Pharmaceuticals (Basel) DOI: 10.3390/ph13070139 sha: doc_id: 260014 cord_uid: q5sug7uu file: cache/cord-261170-arnwk287.json key: cord-261170-arnwk287 authors: Gallimore, W. title: Chapter 18 Marine Metabolites Oceans of Opportunity date: 2017-12-31 journal: Pharmacognosy DOI: 10.1016/b978-0-12-802104-0.00018-4 sha: doc_id: 261170 cord_uid: arnwk287 file: cache/cord-261366-mtcalbo5.json key: cord-261366-mtcalbo5 authors: da Rosa Guimarães, Tatiana; Quiroz, Carlos Guillermo; Rigotto, Caroline; de Oliveira, Simone Quintana; Rojo de Almeida, Maria Tereza; Bianco, Éverson Miguel; Moritz, Maria Izabel Goulart; Carraro, João Luís; Palermo, Jorge Alejandro; Cabrera, Gabriela; Schenkel, Eloir Paulo; Reginatto, Flávio Henrique; Oliveira Simões, Cláudia Maria title: Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae) date: 2013-10-29 journal: Mar Drugs DOI: 10.3390/md11114176 sha: doc_id: 261366 cord_uid: mtcalbo5 file: cache/cord-264316-do0px1gq.json key: cord-264316-do0px1gq authors: Mucha, Artur; Drag, Marcin; Dalton, John P.; Kafarski, Paweł title: Metallo-aminopeptidase inhibitors date: 2010-05-10 journal: Biochimie DOI: 10.1016/j.biochi.2010.04.026 sha: doc_id: 264316 cord_uid: do0px1gq file: cache/cord-270123-m8utyd1m.json key: cord-270123-m8utyd1m authors: Enmozhi, Sukanth Kumar; Raja, Kavitha; Sebastine, Irudhayasamy; Joseph, Jerrine title: Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach date: 2020-05-05 journal: J Biomol Struct Dyn DOI: 10.1080/07391102.2020.1760136 sha: doc_id: 270123 cord_uid: m8utyd1m file: cache/cord-273372-69rlh9or.json key: cord-273372-69rlh9or authors: Litterman, Nadia; Lipinski, Christopher; Ekins, Sean title: Small molecules with antiviral activity against the Ebola virus date: 2015-02-09 journal: F1000Res DOI: 10.12688/f1000research.6120.1 sha: doc_id: 273372 cord_uid: 69rlh9or file: cache/cord-277802-f8pyn3rx.json key: cord-277802-f8pyn3rx authors: Roman, Gheorghe title: Mannich bases in medicinal chemistry and drug design date: 2015-01-07 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2014.10.076 sha: doc_id: 277802 cord_uid: f8pyn3rx file: cache/cord-283128-9mbi75de.json key: cord-283128-9mbi75de authors: Singh, Ramendra K.; Rai, Diwakar; Yadav, Dipti; Bhargava, A.; Balzarini, J.; De Clercq, E. title: Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid date: 2009-12-09 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2009.12.002 sha: doc_id: 283128 cord_uid: 9mbi75de file: cache/cord-283301-adjjkqt2.json key: cord-283301-adjjkqt2 authors: Awolade, Paul; Cele, Nosipho; Kerru, Nagaraju; Gummidi, Lalitha; Oluwakemi, Ebenezer; Singh, Parvesh title: Therapeutic significance of β-glucuronidase activity and its inhibitors: A review date: 2020-02-01 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2019.111921 sha: doc_id: 283301 cord_uid: adjjkqt2 file: cache/cord-290539-8ak2tths.json key: cord-290539-8ak2tths authors: Cagno, Valeria; Tintori, Cristina; Civra, Andrea; Cavalli, Roberta; Tiberi, Marika; Botta, Lorenzo; Brai, Annalaura; Poli, Giulio; Tapparel, Caroline; Lembo, David; Botta, Maurizio title: Novel broad spectrum virucidal molecules against enveloped viruses date: 2018-12-07 journal: PLoS One DOI: 10.1371/journal.pone.0208333 sha: doc_id: 290539 cord_uid: 8ak2tths file: cache/cord-292380-ulsejzqt.json key: cord-292380-ulsejzqt authors: Iwanejko, Jakub; Wojaczyńska, Elżbieta; Turlej, Eliza; Maciejewska, Magdalena; Wietrzyk, Joanna title: Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells date: 2020-05-22 journal: Materials (Basel) DOI: 10.3390/ma13102393 sha: doc_id: 292380 cord_uid: ulsejzqt file: cache/cord-293867-c4wnr5xe.json key: cord-293867-c4wnr5xe authors: Gürsoy, Elif; Dincel, Efe Doğukan; Naesens, Lieve; Ulusoy Güzeldemirci, Nuray title: Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents date: 2019-12-06 journal: Bioorg Chem DOI: 10.1016/j.bioorg.2019.103496 sha: doc_id: 293867 cord_uid: c4wnr5xe file: cache/cord-296560-ehrww6uu.json key: cord-296560-ehrww6uu authors: Bender, Andreas; Jenkins, Jeremy L.; Li, Qingliang; Adams, Sam E.; Cannon, Edward O.; Glen, Robert C. title: Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR date: 2006-11-07 journal: Annu Rep Comput Chem DOI: 10.1016/s1574-1400(06)02009-3 sha: doc_id: 296560 cord_uid: ehrww6uu file: cache/cord-296970-5yc6u5t3.json key: cord-296970-5yc6u5t3 authors: Donmez, Ataberk; Rifaioglu, Ahmet Sureyya; Acar, Aybar; Doğan, Tunca; Cetin-Atalay, Rengul; Atalay, Volkan title: iBioProVis: interactive visualization and analysis of compound bioactivity space date: 2020-08-15 journal: Bioinformatics DOI: 10.1093/bioinformatics/btaa496 sha: doc_id: 296970 cord_uid: 5yc6u5t3 file: cache/cord-300574-nclkfw4h.json key: cord-300574-nclkfw4h authors: Donno, Dario; Mellano, Maria Gabriella; Cerutti, Alessandro Kim; Beccaro, Gabriele Loris title: Chapter 9 Nutraceuticals in Alternative and Underutilized Fruits as Functional Food Ingredients: Ancient Species for New Health Needs date: 2018-12-31 journal: Alternative and Replacement Foods DOI: 10.1016/b978-0-12-811446-9.00009-5 sha: doc_id: 300574 cord_uid: nclkfw4h file: cache/cord-300872-blycbi4u.json key: cord-300872-blycbi4u authors: Saadeh, Haythem A.; Sweidan, Kamal A.; Mubarak, Mohammad S. title: Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines date: 2020-09-21 journal: Molecules DOI: 10.3390/molecules25184321 sha: doc_id: 300872 cord_uid: blycbi4u file: cache/cord-301349-m4nr3pqx.json key: cord-301349-m4nr3pqx authors: Mirza, Muhammad Usman; Saadabadi, Atefeh; Vanmeert, Michiel; Salo-Ahen, Outi M.H.; Abdullah, Iskandar; Claes, Sandra; De Jonghe, Steven; Schols, Dominique; Ahmad, Sarfraz; Froeyen, Matheus title: Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach date: 2020-09-02 journal: Eur J Pharm Sci DOI: 10.1016/j.ejps.2020.105537 sha: doc_id: 301349 cord_uid: m4nr3pqx file: cache/cord-306934-29ljbl7g.json key: cord-306934-29ljbl7g authors: Tonelli, Michele; Vazzana, Iana; Tasso, Bruno; Boido, Vito; Sparatore, Fabio; Fermeglia, Maurizio; Paneni, Maria Silvia; Posocco, Paola; Pricl, Sabrina; Colla, Paolo La; Ibba, Cristina; Secci, Barbara; Collu, Gabriella; Loddo, Roberta title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date: 2009-07-01 journal: Bioorganic & Medicinal Chemistry DOI: 10.1016/j.bmc.2009.05.020 sha: doc_id: 306934 cord_uid: 29ljbl7g file: cache/cord-309052-3h0g7s9v.json key: cord-309052-3h0g7s9v authors: Alam, Fiaz; Khan, Gul Nawaz; Asad, Muhammad Hassham Hassan Bin title: Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review date: 2017-12-15 journal: Phytother Res DOI: 10.1002/ptr.6006 sha: doc_id: 309052 cord_uid: 3h0g7s9v file: cache/cord-315193-z6v6s46n.json key: cord-315193-z6v6s46n authors: Adhikari, Nilanjan; Baidya, Sandip K.; Saha, Achintya; Jha, Tarun title: Structural Insight Into the Viral 3C-Like Protease Inhibitors: Comparative SAR/QSAR Approaches date: 2017-07-14 journal: Viral Proteases and Their Inhibitors DOI: 10.1016/b978-0-12-809712-0.00011-3 sha: doc_id: 315193 cord_uid: z6v6s46n file: cache/cord-317628-1inxq7t5.json key: cord-317628-1inxq7t5 authors: Cuccarese, Michael F.; Earnshaw, Berton A.; Heiser, Katie; Fogelson, Ben; Davis, Chadwick T.; McLean, Peter F.; Gordon, Hannah B.; Skelly, Kathleen-Rose; Weathersby, Fiona L.; Rodic, Vlad; Quigley, Ian K.; Pastuzyn, Elissa D.; Mendivil, Brandon M.; Lazar, Nathan H.; Brooks, Carl A.; Carpenter, Joseph; Probst, Brandon L.; Jacobson, Pamela; Glazier, Seth W.; Ford, Jes; Jensen, James D.; Campbell, Nicholas D.; Statnick, Michael A.; Low, Adeline S.; Thomas, Kirk R.; Carpenter, Anne E.; Hegde, Sharath S.; Alfa, Ronald W.; Victors, Mason L.; Haque, Imran S.; Chong, Yolanda T.; Gibson, Christopher C. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.02.233064 sha: doc_id: 317628 cord_uid: 1inxq7t5 file: cache/cord-318854-xaus3bma.json key: cord-318854-xaus3bma authors: Sun, Yi; Kurokawa, Masahiko; Miura, Motofumi; Kakegawa, Tomohito; Motohashi, Shigeyasu; Yasukawa, Ken title: Chapter 4 Bioactivity and Synthesis of Diarylheptanoids From Alpinia officinarum date: 2016-12-31 journal: Studies in Natural Products Chemistry DOI: 10.1016/b978-0-444-63601-0.00004-1 sha: doc_id: 318854 cord_uid: xaus3bma file: cache/cord-320591-re99v1qt.json key: cord-320591-re99v1qt authors: Le, Thanh Ninh; Chiu, Chiu-Hsia; Hsieh, Pao-Chuan title: Bioactive Compounds and Bioactivities of Brassica oleracea L. var. Italica Sprouts and Microgreens: An Updated Overview from a Nutraceutical Perspective date: 2020-07-27 journal: Plants (Basel) DOI: 10.3390/plants9080946 sha: doc_id: 320591 cord_uid: re99v1qt file: cache/cord-323093-u3ozc9ry.json key: cord-323093-u3ozc9ry authors: Rathnayake, Athri D.; Zheng, Jian; Kim, Yunjeong; Perera, Krishani Dinali; Mackin, Samantha; Meyerholz, David K.; Kashipathy, Maithri M.; Battaile, Kevin P.; Lovell, Scott; Perlman, Stanley; Groutas, William C.; Chang, Kyeong-Ok title: 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date: 2020-08-19 journal: Sci Transl Med DOI: 10.1126/scitranslmed.abc5332 sha: doc_id: 323093 cord_uid: u3ozc9ry file: cache/cord-323479-vlgv3nwq.json key: cord-323479-vlgv3nwq authors: Speranza, Jasmine; Miceli, Natalizia; Taviano, Maria Fernanda; Ragusa, Salvatore; Kwiecień, Inga; Szopa, Agnieszka; Ekiert, Halina title: Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies date: 2020-03-01 journal: Plants (Basel) DOI: 10.3390/plants9030298 sha: doc_id: 323479 cord_uid: vlgv3nwq file: cache/cord-326922-bajpr5a2.json key: cord-326922-bajpr5a2 authors: Watson, C. James; Whitledge, James D.; Siani, Alicia M.; Burns, Michele M. title: Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors date: 2020-11-02 journal: J Med Toxicol DOI: 10.1007/s13181-020-00814-3 sha: doc_id: 326922 cord_uid: bajpr5a2 file: cache/cord-327946-mqakaisa.json key: cord-327946-mqakaisa authors: Massari, Serena; Bertagnin, Chiara; Pismataro, Maria Chiara; Donnadio, Anna; Nannetti, Giulio; Felicetti, Tommaso; Di Bona, Stefano; Nizi, Maria Giulia; Tensi, Leonardo; Manfroni, Giuseppe; Loza, Maria Isabel; Sabatini, Stefano; Cecchetti, Violetta; Brea, Jose; Goracci, Laura; Loregian, Arianna; Tabarrini, Oriana title: Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase date: 2020-10-16 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2020.112944 sha: doc_id: 327946 cord_uid: mqakaisa file: cache/cord-328176-fck2ktxi.json key: cord-328176-fck2ktxi authors: Mahapatra, Manojkumar; Kulandaivelu, Umasankar; Saiko, Philipp; Graser, Geraldine; Szekeres, Thomas; Andrei, Graciela; Snoeck, Robert; Balzarini, Jan; Jayaprakash, Venkatesan title: Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity date: 2013-02-19 journal: Chem Zvesti DOI: 10.2478/s11696-013-0346-4 sha: doc_id: 328176 cord_uid: fck2ktxi file: cache/cord-328834-yetnlb2j.json key: cord-328834-yetnlb2j authors: Mohsin, Noor ul Amin; Irfan, Muhammad; Hassan, Shams ul; Saleem, Usman title: Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review date: 2020-06-15 journal: Pharm Chem J DOI: 10.1007/s11094-020-02187-x sha: doc_id: 328834 cord_uid: yetnlb2j file: cache/cord-328962-1c4vqaqr.json key: cord-328962-1c4vqaqr authors: Benítez-Cardoza, Claudia Guadalupe; Vique-Sánchez, José Luis title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug date: 2020-06-15 journal: Life Sci DOI: 10.1016/j.lfs.2020.117970 sha: doc_id: 328962 cord_uid: 1c4vqaqr file: cache/cord-329078-gnnis7pl.json key: cord-329078-gnnis7pl authors: Musella, Simona; di Sarno, Veronica; Ciaglia, Tania; Sala, Marina; Spensiero, Antonia; Scala, Maria Carmina; Ostacolo, Carmine; Andrei, Graciela; Balzarini, Jan; Snoeck, Robert; Novellino, Ettore; Campiglia, Pietro; Bertamino, Alessia; Gomez-Monterrey, Isabel M. title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor date: 2016-11-29 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2016.09.014 sha: doc_id: 329078 cord_uid: gnnis7pl file: cache/cord-338436-0z828org.json key: cord-338436-0z828org authors: Tzou, Philip L.; Tao, Kaiming; Nouhin, Janin; Rhee, Soo-Yon; Hu, Benjamin D.; Pai, Shruti; Parkin, Neil; Shafer, Robert W. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 journal: Viruses DOI: 10.3390/v12091006 sha: doc_id: 338436 cord_uid: 0z828org file: cache/cord-330465-16j5vm7h.json key: cord-330465-16j5vm7h authors: Marciniec, Krzysztof; Chrobak, Elwira; Dąbrowska, Aleksandra; Bębenek, Ewa; Kadela-Tomanek, Monika; Pęcak, Paweł; Boryczka, Stanisław title: Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study date: 2020-08-05 journal: Biomolecules DOI: 10.3390/biom10081148 sha: doc_id: 330465 cord_uid: 16j5vm7h file: cache/cord-333675-vkk2frnf.json key: cord-333675-vkk2frnf authors: Hamada, Manabu; Roy, Vincent; McBrayer, Tamara R.; Whitaker, Tony; Urbina-Blanco, Cesar; Nolan, Steven P.; Balzarini, Jan; Snoeck, Robert; Andrei, Graciela; Schinazi, Raymond F.; Agrofoglio, Luigi A. title: Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides date: 2013-07-04 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2013.06.053 sha: doc_id: 333675 cord_uid: vkk2frnf file: cache/cord-336759-cu1uprwm.json key: cord-336759-cu1uprwm authors: Cihan-Üstündağ, Gökçe; Naesens, Lieve; Şatana, Dilek; Erköse-Genç, Gonca; Mataracı-Kara, Emel; Çapan, Gültaze title: Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives date: 2019-07-17 journal: Monatsh Chem DOI: 10.1007/s00706-019-02457-9 sha: doc_id: 336759 cord_uid: cu1uprwm file: cache/cord-330994-6nu7utu1.json key: cord-330994-6nu7utu1 authors: Abdelrheem, Doaa A.; Ahmed, Shimaa A.; Abd El-Mageed, H. R.; Mohamed, Hussein S.; Rahman, Aziz A.; Elsayed, Khaled N. M.; Ahmed, Sayed A. title: The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation date: 2020-10-01 journal: Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering DOI: 10.1080/10934529.2020.1826192 sha: doc_id: 330994 cord_uid: 6nu7utu1 file: cache/cord-344598-5drr3fyt.json key: cord-344598-5drr3fyt authors: Khanna, Leena; Singhal, Sugandha; Jain, Subhash C.; Khanna, Pankaj title: Spiro‐Indole‐Coumarin Hybrids: Synthesis, ADME, DFT, NBO Studies and In Silico Screening through Molecular Docking on DNA G‐Quadruplex date: 2020-03-19 journal: ChemistrySelect DOI: 10.1002/slct.201904783 sha: doc_id: 344598 cord_uid: 5drr3fyt file: cache/cord-347547-makm0j09.json key: cord-347547-makm0j09 authors: Duran-Frigola, Miquel; Bertoni, Martino; Blanco, Roi; Martínez, Víctor; Pauls, Eduardo; Alcalde, Víctor; Turon, Gemma; Villegas, Núria; Fernández-Torras, Adrià; Pons, Carles; Mateo, Lídia; Guitart-Pla, Oriol; Badia-i-Mompel, Pau; Gimeno, Aleix; Soler, Nicolas; Brun-Heath, Isabelle; Zaragoza, Hugo; Aloy, Patrick title: Bioactivity Profile Similarities to Expand the Repertoire of COVID-19 Drugs date: 2020-07-16 journal: J Chem Inf Model DOI: 10.1021/acs.jcim.0c00420 sha: doc_id: 347547 cord_uid: makm0j09 file: cache/cord-340832-412qre64.json key: cord-340832-412qre64 authors: Liang, Pi‐Hui; Cheng, Wei‐Chieh; Lee, Yi‐Ling; Yu, Han‐Pang; Wu, Ying‐Ta; Lin, Yi‐Ling; Wong, Chi‐Huey title: Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis date: 2006-01-05 journal: Chembiochem DOI: 10.1002/cbic.200500321 sha: doc_id: 340832 cord_uid: 412qre64 file: cache/cord-340331-51yq1rdo.json key: cord-340331-51yq1rdo authors: Tonelli, Michele; Naesens, Lieve; Gazzarrini, Sabrina; Santucci, Matteo; Cichero, Elena; Tasso, Bruno; Moroni, Anna; Costi, Maria Paola; Loddo, Roberta title: Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus date: 2017-07-28 journal: Eur J Med Chem DOI: 10.1016/j.ejmech.2017.04.070 sha: doc_id: 340331 cord_uid: 51yq1rdo file: cache/cord-345750-dk1exw9l.json key: cord-345750-dk1exw9l authors: Kulikov, A. S.; Epishina, M. A.; Batog, L. V.; Rozhkov, V. Yu.; Makhova, N. N.; Konyushkin, L. D.; Semenova, M. N.; Semenov, V. V. title: Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans date: 2014-01-07 journal: Russ Chem Bull DOI: 10.1007/s11172-013-0113-2 sha: doc_id: 345750 cord_uid: dk1exw9l file: cache/cord-352844-wggg3ynb.json key: cord-352844-wggg3ynb authors: Annunziata, Francesca; Pinna, Cecilia; Dallavalle, Sabrina; Tamborini, Lucia; Pinto, Andrea title: An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities date: 2020-06-29 journal: Int J Mol Sci DOI: 10.3390/ijms21134618 sha: doc_id: 352844 cord_uid: wggg3ynb Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-compound-cord parallel: Warning: Only enough available processes to run 22 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Cannot spawn any jobs. Raising ulimit -u or 'nproc' in /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: No more processes: Decreasing number of running jobs to 21. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: Only enough available processes to run 11 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 8 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 19 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: No more processes: Decreasing number of running jobs to 10. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 7. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 18. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 6. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 17. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 5. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 9. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: Only enough available processes to run 16 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: No more processes: Decreasing number of running jobs to 15. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 16. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 4. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 15. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 8. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 3. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 14. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 13. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50010 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49690 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49746 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50126 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50772 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49747 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50275 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50085 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55019 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50526 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55362 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-025119-201ac32t author: Salman, Saad title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-025119-201ac32t.txt cache: ./cache/cord-025119-201ac32t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-025119-201ac32t.txt' === file2bib.sh === id: cord-014863-jyti99xq author: Karaküçük-İyidoğan, A. title: Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents date: 2019-05-15 pages: extension: .txt txt: ./txt/cord-014863-jyti99xq.txt cache: ./cache/cord-014863-jyti99xq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-014863-jyti99xq.txt' === file2bib.sh === id: cord-253276-mqcwk2ow author: Desai, N. C. title: Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles date: 2013-09-30 pages: extension: .txt txt: ./txt/cord-253276-mqcwk2ow.txt cache: ./cache/cord-253276-mqcwk2ow.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253276-mqcwk2ow.txt' === file2bib.sh === id: cord-255862-84u3c33m author: Kim, Ji Won title: Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut) date: 2017-07-01 pages: extension: .txt txt: ./txt/cord-255862-84u3c33m.txt cache: ./cache/cord-255862-84u3c33m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255862-84u3c33m.txt' === file2bib.sh === id: cord-033493-kslzdy8q author: Hebishy, Ali M. S. title: New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-033493-kslzdy8q.txt cache: ./cache/cord-033493-kslzdy8q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-033493-kslzdy8q.txt' === file2bib.sh === id: cord-034363-6uscua0y author: Cerda-Cavieres, Christopher title: Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands date: 2020-10-10 pages: extension: .txt txt: ./txt/cord-034363-6uscua0y.txt cache: ./cache/cord-034363-6uscua0y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-034363-6uscua0y.txt' === file2bib.sh === id: cord-000445-2x7dfl1q author: Paliwal, Sarvesh K. title: Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances date: 2011-05-10 pages: extension: .txt txt: ./txt/cord-000445-2x7dfl1q.txt cache: ./cache/cord-000445-2x7dfl1q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000445-2x7dfl1q.txt' === file2bib.sh === id: cord-003539-tazd6dvm author: Yang, Kun title: Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration date: 2019-03-02 pages: extension: .txt txt: ./txt/cord-003539-tazd6dvm.txt cache: ./cache/cord-003539-tazd6dvm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003539-tazd6dvm.txt' === file2bib.sh === id: cord-023584-yaxawqhj author: Bucknall, R.A. title: The Continuing Search for Antiviral Drugs date: 2008-04-10 pages: extension: .txt txt: ./txt/cord-023584-yaxawqhj.txt cache: ./cache/cord-023584-yaxawqhj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023584-yaxawqhj.txt' === file2bib.sh === id: cord-103271-l9n27ocf author: Carozza, Jacqueline A title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-103271-l9n27ocf.txt cache: ./cache/cord-103271-l9n27ocf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103271-l9n27ocf.txt' === file2bib.sh === id: cord-260014-q5sug7uu author: Szűcs, Zsolt title: Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-260014-q5sug7uu.txt cache: ./cache/cord-260014-q5sug7uu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260014-q5sug7uu.txt' === file2bib.sh === id: cord-259744-r9j5yzfc author: McDonagh, Phillip title: Identification and characterisation of small molecule inhibitors of feline coronavirus replication date: 2014-12-05 pages: extension: .txt txt: ./txt/cord-259744-r9j5yzfc.txt cache: ./cache/cord-259744-r9j5yzfc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259744-r9j5yzfc.txt' === file2bib.sh === id: cord-013387-q91052qw author: Leão, Rozires P. title: Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-013387-q91052qw.txt cache: ./cache/cord-013387-q91052qw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013387-q91052qw.txt' === file2bib.sh === id: cord-273372-69rlh9or author: Litterman, Nadia title: Small molecules with antiviral activity against the Ebola virus date: 2015-02-09 pages: extension: .txt txt: ./txt/cord-273372-69rlh9or.txt cache: ./cache/cord-273372-69rlh9or.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273372-69rlh9or.txt' === file2bib.sh === id: cord-261366-mtcalbo5 author: da Rosa Guimarães, Tatiana title: Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae) date: 2013-10-29 pages: extension: .txt txt: ./txt/cord-261366-mtcalbo5.txt cache: ./cache/cord-261366-mtcalbo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261366-mtcalbo5.txt' === file2bib.sh === id: cord-270123-m8utyd1m author: Enmozhi, Sukanth Kumar title: Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-270123-m8utyd1m.txt cache: ./cache/cord-270123-m8utyd1m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270123-m8utyd1m.txt' === file2bib.sh === id: cord-261170-arnwk287 author: Gallimore, W. title: Chapter 18 Marine Metabolites Oceans of Opportunity date: 2017-12-31 pages: extension: .txt txt: ./txt/cord-261170-arnwk287.txt cache: ./cache/cord-261170-arnwk287.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261170-arnwk287.txt' === file2bib.sh === id: cord-021419-nypnib0h author: Olsufyeva, Evgenia N. title: Main trends in the design of semi-synthetic antibiotics of a new generation date: 2020-03-17 pages: extension: .txt txt: ./txt/cord-021419-nypnib0h.txt cache: ./cache/cord-021419-nypnib0h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-021419-nypnib0h.txt' === file2bib.sh === id: cord-283128-9mbi75de author: Singh, Ramendra K. title: Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid date: 2009-12-09 pages: extension: .txt txt: ./txt/cord-283128-9mbi75de.txt cache: ./cache/cord-283128-9mbi75de.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283128-9mbi75de.txt' === file2bib.sh === id: cord-296970-5yc6u5t3 author: Donmez, Ataberk title: iBioProVis: interactive visualization and analysis of compound bioactivity space date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-296970-5yc6u5t3.txt cache: ./cache/cord-296970-5yc6u5t3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296970-5yc6u5t3.txt' === file2bib.sh === id: cord-293867-c4wnr5xe author: Gürsoy, Elif title: Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents date: 2019-12-06 pages: extension: .txt txt: ./txt/cord-293867-c4wnr5xe.txt cache: ./cache/cord-293867-c4wnr5xe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293867-c4wnr5xe.txt' === file2bib.sh === id: cord-290539-8ak2tths author: Cagno, Valeria title: Novel broad spectrum virucidal molecules against enveloped viruses date: 2018-12-07 pages: extension: .txt txt: ./txt/cord-290539-8ak2tths.txt cache: ./cache/cord-290539-8ak2tths.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-290539-8ak2tths.txt' === file2bib.sh === id: cord-017041-0zxoq68m author: Volochnyuk, Dmitriy M. title: Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry date: 2014-06-13 pages: extension: .txt txt: ./txt/cord-017041-0zxoq68m.txt cache: ./cache/cord-017041-0zxoq68m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-017041-0zxoq68m.txt' === file2bib.sh === id: cord-292380-ulsejzqt author: Iwanejko, Jakub title: Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-292380-ulsejzqt.txt cache: ./cache/cord-292380-ulsejzqt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-292380-ulsejzqt.txt' === file2bib.sh === id: cord-023284-i0ecxgus author: nan title: Abstracts of publications related to QASR date: 2006-09-19 pages: extension: .txt txt: ./txt/cord-023284-i0ecxgus.txt cache: ./cache/cord-023284-i0ecxgus.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023284-i0ecxgus.txt' === file2bib.sh === id: cord-300574-nclkfw4h author: Donno, Dario title: Chapter 9 Nutraceuticals in Alternative and Underutilized Fruits as Functional Food Ingredients: Ancient Species for New Health Needs date: 2018-12-31 pages: extension: .txt txt: ./txt/cord-300574-nclkfw4h.txt cache: ./cache/cord-300574-nclkfw4h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300574-nclkfw4h.txt' === file2bib.sh === id: cord-264316-do0px1gq author: Mucha, Artur title: Metallo-aminopeptidase inhibitors date: 2010-05-10 pages: extension: .txt txt: ./txt/cord-264316-do0px1gq.txt cache: ./cache/cord-264316-do0px1gq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-264316-do0px1gq.txt' === file2bib.sh === id: cord-296560-ehrww6uu author: Bender, Andreas title: Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR date: 2006-11-07 pages: extension: .txt txt: ./txt/cord-296560-ehrww6uu.txt cache: ./cache/cord-296560-ehrww6uu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296560-ehrww6uu.txt' === file2bib.sh === id: cord-301349-m4nr3pqx author: Mirza, Muhammad Usman title: Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-301349-m4nr3pqx.txt cache: ./cache/cord-301349-m4nr3pqx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301349-m4nr3pqx.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-024652-4i6kktl0 author: Santra, Hiran Kanti title: Natural Products as Fungicide and Their Role in Crop Protection date: 2020-05-12 pages: extension: .txt txt: ./txt/cord-024652-4i6kktl0.txt cache: ./cache/cord-024652-4i6kktl0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-024652-4i6kktl0.txt' === file2bib.sh === id: cord-315193-z6v6s46n author: Adhikari, Nilanjan title: Structural Insight Into the Viral 3C-Like Protease Inhibitors: Comparative SAR/QSAR Approaches date: 2017-07-14 pages: extension: .txt txt: ./txt/cord-315193-z6v6s46n.txt cache: ./cache/cord-315193-z6v6s46n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315193-z6v6s46n.txt' === file2bib.sh === id: cord-318854-xaus3bma author: Sun, Yi title: Chapter 4 Bioactivity and Synthesis of Diarylheptanoids From Alpinia officinarum date: 2016-12-31 pages: extension: .txt txt: ./txt/cord-318854-xaus3bma.txt cache: ./cache/cord-318854-xaus3bma.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318854-xaus3bma.txt' === file2bib.sh === id: cord-327946-mqakaisa author: Massari, Serena title: Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-327946-mqakaisa.txt cache: ./cache/cord-327946-mqakaisa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327946-mqakaisa.txt' === file2bib.sh === id: cord-306934-29ljbl7g author: Tonelli, Michele title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date: 2009-07-01 pages: extension: .txt txt: ./txt/cord-306934-29ljbl7g.txt cache: ./cache/cord-306934-29ljbl7g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306934-29ljbl7g.txt' === file2bib.sh === id: cord-328176-fck2ktxi author: Mahapatra, Manojkumar title: Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity date: 2013-02-19 pages: extension: .txt txt: ./txt/cord-328176-fck2ktxi.txt cache: ./cache/cord-328176-fck2ktxi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-328176-fck2ktxi.txt' === file2bib.sh === id: cord-309052-3h0g7s9v author: Alam, Fiaz title: Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review date: 2017-12-15 pages: extension: .txt txt: ./txt/cord-309052-3h0g7s9v.txt cache: ./cache/cord-309052-3h0g7s9v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309052-3h0g7s9v.txt' === file2bib.sh === id: cord-323093-u3ozc9ry author: Rathnayake, Athri D. title: 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-323093-u3ozc9ry.txt cache: ./cache/cord-323093-u3ozc9ry.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323093-u3ozc9ry.txt' === file2bib.sh === id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-317628-1inxq7t5.txt cache: ./cache/cord-317628-1inxq7t5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317628-1inxq7t5.txt' === file2bib.sh === id: cord-326922-bajpr5a2 author: Watson, C. James title: Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-326922-bajpr5a2.txt cache: ./cache/cord-326922-bajpr5a2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326922-bajpr5a2.txt' === file2bib.sh === id: cord-320591-re99v1qt author: Le, Thanh Ninh title: Bioactive Compounds and Bioactivities of Brassica oleracea L. var. Italica Sprouts and Microgreens: An Updated Overview from a Nutraceutical Perspective date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-320591-re99v1qt.txt cache: ./cache/cord-320591-re99v1qt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320591-re99v1qt.txt' === file2bib.sh === id: cord-328834-yetnlb2j author: Mohsin, Noor ul Amin title: Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-328834-yetnlb2j.txt cache: ./cache/cord-328834-yetnlb2j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328834-yetnlb2j.txt' === file2bib.sh === id: cord-328962-1c4vqaqr author: Benítez-Cardoza, Claudia Guadalupe title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-328962-1c4vqaqr.txt cache: ./cache/cord-328962-1c4vqaqr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-328962-1c4vqaqr.txt' === file2bib.sh === id: cord-300872-blycbi4u author: Saadeh, Haythem A. title: Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-300872-blycbi4u.txt cache: ./cache/cord-300872-blycbi4u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300872-blycbi4u.txt' === file2bib.sh === id: cord-283301-adjjkqt2 author: Awolade, Paul title: Therapeutic significance of β-glucuronidase activity and its inhibitors: A review date: 2020-02-01 pages: extension: .txt txt: ./txt/cord-283301-adjjkqt2.txt cache: ./cache/cord-283301-adjjkqt2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283301-adjjkqt2.txt' === file2bib.sh === id: cord-329078-gnnis7pl author: Musella, Simona title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor date: 2016-11-29 pages: extension: .txt txt: ./txt/cord-329078-gnnis7pl.txt cache: ./cache/cord-329078-gnnis7pl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-329078-gnnis7pl.txt' === file2bib.sh === id: cord-347547-makm0j09 author: Duran-Frigola, Miquel title: Bioactivity Profile Similarities to Expand the Repertoire of COVID-19 Drugs date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-347547-makm0j09.txt cache: ./cache/cord-347547-makm0j09.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347547-makm0j09.txt' === file2bib.sh === id: cord-336759-cu1uprwm author: Cihan-Üstündağ, Gökçe title: Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives date: 2019-07-17 pages: extension: .txt txt: ./txt/cord-336759-cu1uprwm.txt cache: ./cache/cord-336759-cu1uprwm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336759-cu1uprwm.txt' === file2bib.sh === id: cord-344598-5drr3fyt author: Khanna, Leena title: Spiro‐Indole‐Coumarin Hybrids: Synthesis, ADME, DFT, NBO Studies and In Silico Screening through Molecular Docking on DNA G‐Quadruplex date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-344598-5drr3fyt.txt cache: ./cache/cord-344598-5drr3fyt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344598-5drr3fyt.txt' === file2bib.sh === id: cord-340832-412qre64 author: Liang, Pi‐Hui title: Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis date: 2006-01-05 pages: extension: .txt txt: ./txt/cord-340832-412qre64.txt cache: ./cache/cord-340832-412qre64.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340832-412qre64.txt' === file2bib.sh === id: cord-323479-vlgv3nwq author: Speranza, Jasmine title: Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies date: 2020-03-01 pages: extension: .txt txt: ./txt/cord-323479-vlgv3nwq.txt cache: ./cache/cord-323479-vlgv3nwq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323479-vlgv3nwq.txt' === file2bib.sh === id: cord-333675-vkk2frnf author: Hamada, Manabu title: Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides date: 2013-07-04 pages: extension: .txt txt: ./txt/cord-333675-vkk2frnf.txt cache: ./cache/cord-333675-vkk2frnf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333675-vkk2frnf.txt' === file2bib.sh === id: cord-345750-dk1exw9l author: Kulikov, A. S. title: Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans date: 2014-01-07 pages: extension: .txt txt: ./txt/cord-345750-dk1exw9l.txt cache: ./cache/cord-345750-dk1exw9l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-345750-dk1exw9l.txt' === file2bib.sh === id: cord-330994-6nu7utu1 author: Abdelrheem, Doaa A. title: The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-330994-6nu7utu1.txt cache: ./cache/cord-330994-6nu7utu1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330994-6nu7utu1.txt' === file2bib.sh === id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-338436-0z828org.txt cache: ./cache/cord-338436-0z828org.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338436-0z828org.txt' === file2bib.sh === id: cord-330465-16j5vm7h author: Marciniec, Krzysztof title: Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-330465-16j5vm7h.txt cache: ./cache/cord-330465-16j5vm7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330465-16j5vm7h.txt' === file2bib.sh === id: cord-340331-51yq1rdo author: Tonelli, Michele title: Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus date: 2017-07-28 pages: extension: .txt txt: ./txt/cord-340331-51yq1rdo.txt cache: ./cache/cord-340331-51yq1rdo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340331-51yq1rdo.txt' === file2bib.sh === id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 pages: extension: .txt txt: ./txt/cord-020010-q58x6xb0.txt cache: ./cache/cord-020010-q58x6xb0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-020010-q58x6xb0.txt' === file2bib.sh === id: cord-352844-wggg3ynb author: Annunziata, Francesca title: An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-352844-wggg3ynb.txt cache: ./cache/cord-352844-wggg3ynb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-352844-wggg3ynb.txt' === file2bib.sh === id: cord-277802-f8pyn3rx author: Roman, Gheorghe title: Mannich bases in medicinal chemistry and drug design date: 2015-01-07 pages: extension: .txt txt: ./txt/cord-277802-f8pyn3rx.txt cache: ./cache/cord-277802-f8pyn3rx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-277802-f8pyn3rx.txt' Que is empty; done keyword-compound-cord === reduce.pl bib === id = cord-000445-2x7dfl1q author = Paliwal, Sarvesh K. title = Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances date = 2011-05-10 pages = extension = .txt mime = text/plain words = 8603 sentences = 401 flesch = 44 summary = brucei rhodesiense than the corresponding 2,5-substituted isomers (compounds 1-10, figure 4a), while among the 2, 5-substituted dications, the compounds possessing cationic substituents adjacent to nitrogen atoms in pyridine rings displayed superior activities against parasites compared to pentamidine as evident from compound 6 (figure 4b) which showed promising anti-trypanosomal activity (0.001µM) and lower cytotoxicity (4.90µM) than pentamidine and melarsoprol, but had poor in vivo activity giving only 1/4 cures in the STIB900 mouse model. Structure of two phenylbenzofuran dications with promising anti-trypanosomal activity Tidwell RR et al found that the in vitro anti-trypanosomal activities of bisbenzofuran derivatives against Trypanosoma brucei rhodesiense, and cytotoxicity against mammalian cells depended on the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. Thus promising in vitro, anti-trypanosomal activity, excellent potency in the acute mouse model of trypanosomiasis and the reduced cytotoxicity (1.9 µM) of compound 1 compared to pentamidine warrants further pre-clinical and clinical trials of this molecule. cache = ./cache/cord-000445-2x7dfl1q.txt txt = ./txt/cord-000445-2x7dfl1q.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-013387-q91052qw author = Leão, Rozires P. title = Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach date = 2020-08-26 pages = extension = .txt mime = text/plain words = 12136 sentences = 651 flesch = 43 summary = In this initial stage, the pivot molecule rofecoxib was used as a research model for the virtual screening in six commercial molecule databases: Chembridge DIVERSetEXP, DIVERSet CORE Library (https://www.chembridge.com) [24] , Maybridge Collections (www.maybridge.com) [25, 26] , ZINC Drug Database, ZINC Natural Stock (http://zinc.docking.org) [27] , and Drug FDA BindingDB (http://www.bindingdb.org) [27] using the programs Rapid Overlay of Chemical Structures (ROCS) and electrostatic similarity (EON). The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity. The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity. cache = ./cache/cord-013387-q91052qw.txt txt = ./txt/cord-013387-q91052qw.txt === reduce.pl bib === id = cord-003539-tazd6dvm author = Yang, Kun title = Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration date = 2019-03-02 pages = extension = .txt mime = text/plain words = 9249 sentences = 483 flesch = 51 summary = According to the general procedure A, compound 2 was treated with 1-(Boc-amino)cyclopropanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3k: Yellow solid; yield, 28%; 1 H-NMR δ 11.96 (brs, 1H), 8 189.28, 180.10, 169.83, 164.69, 164.22, 161.39, 148.39, 134.15, 132.07, 123.98, 120.37, 112.73, 109.54, 107.67, 106.74, 66.57, 63.78 1-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)cyclobutan-aminium 2,2,2-trifluoroacetate (3l). According to the general procedure A, compound 2 was treated with 1-(Boc-amino)cyclobutanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3l: Yellow solid; yield, 28%; 1 H-NMR δ 11.95 (brs, 1H), 8 3-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)oxetan-3-aminium 2,2,2-trifluoroacetate (3m). According to the general procedure A, compound 2 was treated with 3-Boc-amino-3-oxetanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3m: Yellow solid; yield, 37%; 1 H-NMR δ 11.97 (brs, 2H), 8 1-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)cyclopentan-aminium 2,2,2-trifluoroacetate (3n). cache = ./cache/cord-003539-tazd6dvm.txt txt = ./txt/cord-003539-tazd6dvm.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-014863-jyti99xq author = Karaküçük-İyidoğan, A. title = Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents date = 2019-05-15 pages = extension = .txt mime = text/plain words = 3517 sentences = 516 flesch = 69 summary = Encouraged by these results and aimed at developing effective anticancer agents, we designed two series of thiosemicarbazones by the pharmacophore hybridization method using two or more different pharmacophores in view of prospecting their cytostatic and antiviral activity (Fig. 1) . The synthesized compounds were also evaluated for their cytostatic activity against murine leukemia L1210, human CD 4 + T-lymphocyte CEM and cervix carcinoma HeLa cells (Table 4 ). The results showed that compounds Ia -Ig containing electron-withdrawing group, such as -CN located at the para position of the benzene ring, increased the cytostatic activity, according to the electron-donating group (-SCH 3 ) at the same position of the structure (like compounds Synthesis, Biological Evaluation and Ligand 147 IIa -IIg). It is established that Hb-acceptor (-CN; -SCH 3 ), hydrophobic groups (-N(CH 2 CH 2 Cl) 2 ), and 3D-conformations are responsible for the cytostatic activity of compounds such as Ig and IIg, according to ligand-based pharmacophore modeling. cache = ./cache/cord-014863-jyti99xq.txt txt = ./txt/cord-014863-jyti99xq.txt === reduce.pl bib === id = cord-017041-0zxoq68m author = Volochnyuk, Dmitriy M. title = Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry date = 2014-06-13 pages = extension = .txt mime = text/plain words = 16251 sentences = 955 flesch = 47 summary = Herein we give a comprehensive review on the biological activity and synthesis of fluorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry. Herein we give a comprehensive review on the biological activity and synthesis of fl uorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry. In an alternative approach, Fluorouracil was prepared by direct fl uorination of different pyrimidine derivatives, including uracil [ 15 ] , cytosine [ 16 ] , and orotic acid [ 17 ] . Early synthesis of Floxuridine commenced from Fluorouracil ( 1 ) which was transformed into its mercury salt 28 and then allowed to react with 2-deoxy-Dribofuranosyl chloride derivative 29 (Scheme 4 ) [ 18 ] . More precisely, Trifl uridine is transformed into α,α,α-trifl uorothymidine monophosphate ( 76 ) by thymidine kinase (Scheme 21 ); similarly to the Fluorouracil derivatives discussed in the previous sections, compound 76 is true inhibitor of thymidylate synthase. cache = ./cache/cord-017041-0zxoq68m.txt txt = ./txt/cord-017041-0zxoq68m.txt === reduce.pl bib === === reduce.pl bib === id = cord-021419-nypnib0h author = Olsufyeva, Evgenia N. title = Main trends in the design of semi-synthetic antibiotics of a new generation date = 2020-03-17 pages = extension = .txt mime = text/plain words = 16144 sentences = 923 flesch = 45 summary = In this review, the following classes of compounds are considered as scaffolds for the synthesis of new antibiotics: polycyclic glycopeptides of the vancomycin ± teicoplanin group, classical macrolides, macrolides of the amphotericin B ± oligomycin group, anthracyclines, aureolic acid derivatives, heliomycin, synthetic benzoxaboroles and some other antibiotics. 42 Antibacterial activity of derivatives 52 ± 55 modified at the C(11)7OH group of the aglycone was evaluated compared to the starting antibiotics vancomycin (1) and azithromycin (30) on a panel of Gram-positive and Gramnegative bacterial strains (8 and 3 strains, respectively). In order to improve antifungal properties, cytotoxic and therapeutic characteristics and to study the mechanisms of action, series of new semi-synthetic derivatives based on AmB (63a) and bioengineered analogues S44HP (64a), BSG005 (65a), BSG022 (66a), BSG019 (67), BSG003 (68a) and BSG018 (69) were synthesized (in collaboration with the company BIOSERGEN, Norway) (Scheme 17). cache = ./cache/cord-021419-nypnib0h.txt txt = ./txt/cord-021419-nypnib0h.txt === reduce.pl bib === id = cord-023284-i0ecxgus author = nan title = Abstracts of publications related to QASR date = 2006-09-19 pages = extension = .txt mime = text/plain words = 19803 sentences = 1320 flesch = 48 summary = Results: Methods developed for the investigation for the relationships between structure and toxic effects of compounds are summarized: a) The extra-thermodynamic approach: the Hansch paradigm, physical chemical properties that influence biological activity and their parametrization, originality of the Hansch approach, receptors and pharmacophores: the natural content of the Hansch approach, predictive value of QSARs, a statistifa1 tool: multiple linear regression analysis, the problem of correlations among molecular descriptors, other mathematical utilizations of extrathermodynamic parameters; b) The substructural approach: when topological (substructural) descriptors are needed, how to use topological decriptors; c) QSAR in mutagenicity and carcinogenicity: general problems, specific versions of the substructural approach used for mutagenicity and carcinogenicity, applications to mutagenicity and carcinogenicity. cache = ./cache/cord-023284-i0ecxgus.txt txt = ./txt/cord-023284-i0ecxgus.txt === reduce.pl bib === id = cord-023584-yaxawqhj author = Bucknall, R.A. title = The Continuing Search for Antiviral Drugs date = 2008-04-10 pages = extension = .txt mime = text/plain words = 8497 sentences = 339 flesch = 48 summary = Of course, if wide-spectrum leads appear, the choice of test virus may be irrelevant, but the antiviral compounds (as distinct from interferon inducers) known at present are characterized by their relatively limited spectrum of activity, e.g., methisazone is active only against poxviruses (Bauer and Sadler, 1960) and possibly adenoviruses (Bauer and Apostolov, 1966) ; l-aminoadamantane is active only against influenza A1 and As and not against other myxo-or paramyxoviruses (Davies et al., 1964) ; guanidine and a-hydroxybenzyl benzimidazole are active only against picornaviruses and not against other small ribonucleic acid (RNA) viruses (Eggers and Tamm, 1961) . In summary, a tissue culture screen should be able to proccss large numbers of tcst compounds, using viruses as relevant as possible to the diseases for which a drug is required, and should employ normal rather than neoplastic cells. cache = ./cache/cord-023584-yaxawqhj.txt txt = ./txt/cord-023584-yaxawqhj.txt === reduce.pl bib === id = cord-025119-201ac32t author = Salman, Saad title = Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date = 2020-05-21 pages = extension = .txt mime = text/plain words = 3144 sentences = 162 flesch = 37 summary = Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Here, we analyzed different medicinal compounds using a virtual screening method to obtain promising inhibitors for these viral proteins that could be further utilized for SARS-COV-2 treatment. More than 300 medicinal compounds with immunomodulatory and antiviral activity were added to the Raccoon2 plugin of Autodock vina to perform virtual screening to obtain promising inhibitors for SARS-COV-2 proteins. This study aimed to obtain novel drug candidates that have the capability to interact with the active site of all of these viral proteins and should possess efficient pharmacokinetic profile with low toxicity to ensure safety during administration. • Docking interaction of immunomodulatory medicinal compounds library filtered six promising medicinal compounds against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) viral proteins. cache = ./cache/cord-025119-201ac32t.txt txt = ./txt/cord-025119-201ac32t.txt === reduce.pl bib === === reduce.pl bib === id = cord-034363-6uscua0y author = Cerda-Cavieres, Christopher title = Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands date = 2020-10-10 pages = extension = .txt mime = text/plain words = 7540 sentences = 384 flesch = 52 summary = title: Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D(2) receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). Considering the pharmacological results, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds were carried out only in the human SERT (hSERT) and in selected cases at the D 2 receptor. Considering the pharmacological results, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds were carried out only in the human SERT (hSERT) and in selected cases at the D 2 receptor. cache = ./cache/cord-034363-6uscua0y.txt txt = ./txt/cord-034363-6uscua0y.txt === reduce.pl bib === id = cord-020010-q58x6xb0 author = nan title = 19th ICAR Abstracts: date = 2006-03-13 pages = extension = .txt mime = text/plain words = 46663 sentences = 2181 flesch = 44 summary = In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. cache = ./cache/cord-020010-q58x6xb0.txt txt = ./txt/cord-020010-q58x6xb0.txt === reduce.pl bib === id = cord-024652-4i6kktl0 author = Santra, Hiran Kanti title = Natural Products as Fungicide and Their Role in Crop Protection date = 2020-05-12 pages = extension = .txt mime = text/plain words = 20643 sentences = 1184 flesch = 39 summary = A large number of bioactive compounds ranging from direct plant (both cryptogams algae and moss and phanerogams)-derived natural extracts, essential oil of aromatic plants, and low-molecular-weight antimicrobial compounds known as phytoalexins to secondary metabolites that are both volatile and nonvolatile organic compounds of microbes (fungal and actinobacterial members) residing inside the host tissue, called endophyte, are widely used as agricultural bioweapons. Endophytic culture extracts are also known to be rich sources of phenolics; usually they are directly proportional to the antioxidative property of any fungal isolate, but in some particular cases, they are characterized with their antifungal potentials against phytopathogenic fungus. So it is a great opportunity to use the unique mixture of volatile organic compounds of the endophytic isolate to reduce the crop loss caused by the pathogenic infection on the commercially valuable plant of cherry tomato worldwide. cache = ./cache/cord-024652-4i6kktl0.txt txt = ./txt/cord-024652-4i6kktl0.txt === reduce.pl bib === id = cord-103271-l9n27ocf author = Carozza, Jacqueline A title = Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date = 2020-05-31 pages = extension = .txt mime = text/plain words = 5664 sentences = 329 flesch = 51 summary = Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. Inspired by the molecular scaffold of a previous inhibitor, QS1, 26, 28 which lacks potency at physiological conditions, we build structure-activity relationships (SAR) around the three sections of the molecule -the zinc-binding head, the core, and the tail -and develop several inhibitors with nanomolar Ki values. Assays used to assess the potency of previously attempted ENPP1 inhibitors are inconsistent 26-34 ; however, developing an appropriate assay is key to determining the utility of the molecules in inhibiting cGAMP degradation under physiological conditions. Since our crystal structure suggests that the zinc-binding phosphonate head and quinazoline tail form the most important interactions with ENPP1, we next sought to explore the core region to achieve optimal geometry between these two functional groups ( Fig. 4a-b) . cache = ./cache/cord-103271-l9n27ocf.txt txt = ./txt/cord-103271-l9n27ocf.txt === reduce.pl bib === id = cord-033493-kslzdy8q author = Hebishy, Ali M. S. title = New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity date = 2020-09-21 pages = extension = .txt mime = text/plain words = 3385 sentences = 186 flesch = 50 summary = title: New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity [Image: see text] This study describes a new route to the synthesis of novel benzamide-based 5-aminopyrazoles and their corresponding pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives. 5-Aminopyrazole 4 was prepared by alkylation of the potassium 2-cyano-ethylene-1thiolate salt 2 with an alkyl halide at room temperature to offer N-(2,2-dicyano-1-(alkylthio)vinyl)benzamide 3 followed by a reaction with hydrazine hydrate by refluxing ethanol containing a catalytic amount of piperidine (Scheme 1). The antiviral activity was measured for the synthesized compounds with respect to the H5N1 influenza virus strain A/Egypt/M7217B/2013 using MTT 50 ) and plaque reduction assays 52 exploring the cytotoxicity and inhibition percentage values, respectively. Design, synthesis, docking, and antimicrobial evaluation of some novel pyrazolo[1,5-a] pyrimidines and their corresponding cycloalkane ring-fused derivatives as purine analogs cache = ./cache/cord-033493-kslzdy8q.txt txt = ./txt/cord-033493-kslzdy8q.txt === reduce.pl bib === === reduce.pl bib === id = cord-253276-mqcwk2ow author = Desai, N. C. title = Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles date = 2013-09-30 pages = extension = .txt mime = text/plain words = 2623 sentences = 155 flesch = 47 summary = The structure activity relationship revealed that the presence of electron withdrawing groups at para position of phenyl ring remarkably enhanced the antibacterial activity of synthesized compounds. From the results of the antimicrobial activity of the synthesized compounds 5ael, the following structure activity relationships can be derived: the antibacterial activity was considerably affected by substitution pattern on the phenyl ring and the most active compounds contain electron withdrawing substituent at para and meta positions of the phenyl ring (p > m > o). Compounds 5c and 5i, substituted with inductively electron withdrawing fluoro and nitro groups, respectively at para position showed the highest antibacterial activity (F > NO 2 ). While, substituting the phenyl ring with fluoro and nitro group at ortho position resulted in noticeable decrease in the antibacterial activity of compounds 5a and 5g respectively. The contrasting nature of substitution pattern at para position of the phenyl ring of most active antibacterial and antifungal agents indicate that the structural requirements are different for binding of drug to bacterial or fungal targets, respectively [43] . cache = ./cache/cord-253276-mqcwk2ow.txt txt = ./txt/cord-253276-mqcwk2ow.txt === reduce.pl bib === === reduce.pl bib === id = cord-255862-84u3c33m author = Kim, Ji Won title = Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut) date = 2017-07-01 pages = extension = .txt mime = text/plain words = 2843 sentences = 172 flesch = 61 summary = In this research, we investigated whether escin derivatives 1–7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Interestingly, compounds 1-7 isolated from the fraction with the two-step hydrolysis were evaluated to have much lower cytotoxic effects than compounds 8-10 from the n-BuOH part at concentration of 20 lM (Fig. S22) . As compounds 8-10 showed strong cytotoxic effects on Vero cells at 20 lM, their PEDV inhibitory activities were evaluated at a concentration of 2 lM. 33 To measure the expression level of viral RNA encoding nucleocapsid and spike proteins, compounds 4 and 6 were treated in Vero cells at a concentration of 40 lM and total RNA was extracted for reverse transcription followed by polymerase chain reaction using the primers for PEDV (STable 1 ). cache = ./cache/cord-255862-84u3c33m.txt txt = ./txt/cord-255862-84u3c33m.txt === reduce.pl bib === id = cord-260014-q5sug7uu author = Szűcs, Zsolt title = Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity date = 2020-06-29 pages = extension = .txt mime = text/plain words = 5179 sentences = 333 flesch = 51 summary = We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. On the other hand, this result is in line with our previous findings on ristocetin and teicoplanin aglycone derivatives, indicating that even minor structural differences in the peptide core can lead to significantly different anti-influenza virus activity [27] . On the other hand, this result is in line with our previous findings on ristocetin and teicoplanin aglycone derivatives, indicating that even minor structural differences in the peptide core can lead to significantly different anti-influenza virus activity [27] . Hence, we established, by virus yield assays, that compound 6 suppresses the replication of influenza virus and coronavirus, and for the other viruses, activity was indicated by the protection against viral CPE. Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: An aggregation and receptor binding study cache = ./cache/cord-260014-q5sug7uu.txt txt = ./txt/cord-260014-q5sug7uu.txt === reduce.pl bib === id = cord-259744-r9j5yzfc author = McDonagh, Phillip title = Identification and characterisation of small molecule inhibitors of feline coronavirus replication date = 2014-12-05 pages = extension = .txt mime = text/plain words = 5636 sentences = 258 flesch = 41 summary = Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. This study identifies three compounds (chloroquine, mefloquine, and hexamethylene amiloride) demonstrating a marked inhibitory effect on FCoV replication in vitro by significant reductions in virus induced CPE and viral titres at low micromolar concentrations when present during the early stages of viral replication. This study has identified three compounds demonstrating marked in vitro inhibition of FCoV in an immortalised cell line at low micromolar concentrations, including the first demonstration of antiviral effects of mefloquine against a coronavirus. cache = ./cache/cord-259744-r9j5yzfc.txt txt = ./txt/cord-259744-r9j5yzfc.txt === reduce.pl bib === id = cord-261366-mtcalbo5 author = da Rosa Guimarães, Tatiana title = Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae) date = 2013-10-29 pages = extension = .txt mime = text/plain words = 4824 sentences = 269 flesch = 54 summary = The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. In a previous screening of the anti-infective potential of marine invertebrates and seaweeds [28] , we observed a promising activity for the n-butanol fraction (BF) obtained from the ethanolic crude extract of this sponge that led us to perform this study. As it is important to understand the targets and the mode of action of a potential useful new antiviral agent, a set of experiments was carried out to determine the stages at which the most active samples (TSH fraction and compounds 1 and 2) affect the viral replication cycle. cache = ./cache/cord-261366-mtcalbo5.txt txt = ./txt/cord-261366-mtcalbo5.txt === reduce.pl bib === id = cord-261170-arnwk287 author = Gallimore, W. title = Chapter 18 Marine Metabolites Oceans of Opportunity date = 2017-12-31 pages = extension = .txt mime = text/plain words = 7118 sentences = 404 flesch = 41 summary = Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. To gain an understanding of the importance of marine natural products chemistry in drug development G To be able to map the process involved in drug development from marine natural products G To gain an appreciation of the range of biological activities associated with compounds isolated from micro-and macroorganisms G To identify the marine-derived drugs which are undergoing clinical evaluation Biological activities identified in extracts and metabolites of algal origin include anticancer, antiobesity, neuroprotective, and antioxidant activity and Scheme 18.2 shows chemical structures of representative bioactive compounds isolated from the macroalgae. Biologically active compounds from marine bacteria also include Streptomyces species from sediment and fish gut from which anticancer (e.g., halichomycin and δ-indomycinone) and antibacterial agents (e.g., phenazines) have been obtained [58À60]. cache = ./cache/cord-261170-arnwk287.txt txt = ./txt/cord-261170-arnwk287.txt === reduce.pl bib === id = cord-264316-do0px1gq author = Mucha, Artur title = Metallo-aminopeptidase inhibitors date = 2010-05-10 pages = extension = .txt mime = text/plain words = 14674 sentences = 769 flesch = 41 summary = This review focuses on the strict metallo-aminopeptidases because they constitute the largest and the most homogenous class of these enzymes and use one or two metal ions in their active sites to specifically release the N-terminal amino acid residues of polypeptides and proteins. Similar to other amino acid and peptide mimetics used as protease inhibitors, this is the effect of the incorporation of a covalent or non-covalent binding group (here involved in coordination of a catalytic metal ion(s) in the enzyme active site) into a substrate structure. Additionally, the P1 side chain of the aminophosphonic acid analogues (or more effectively, both P1 and P1 0 residues of the pseudopeptides phosphoryl moiety) gives further possibility of structural optimization of substituents interacting with the S1 and S1 0 binding pockets of the enzyme (Fig. 3) Fig. 4 ), appeared to be efficient inhibitors of LAP with a K i ¼ 0.15 [90] and 0.23 mM [87] for the R (L) enantiomers. cache = ./cache/cord-264316-do0px1gq.txt txt = ./txt/cord-264316-do0px1gq.txt === reduce.pl bib === id = cord-270123-m8utyd1m author = Enmozhi, Sukanth Kumar title = Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach date = 2020-05-05 pages = extension = .txt mime = text/plain words = 3873 sentences = 187 flesch = 49 summary = This paper evaluates the compound Andrographolide from Andrographis paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction and ADME prediction. And upon certain in vitro and some clinical data chloroquine phosphate and hydroxychloroquine sulphate was advised to be the treatment for COVID-19 and enough randomized trials on these compounds to be provided and allowed the administration of the above drugs to be used for emergency (https://www.fda.gov/emergency-use-authori-zation#covidtherapeutics). Though there are many targets are found for the treatment of COVID-19, the main protease (M pro ) of SARS-CoV-2 was chosen due to interest of treating infected patients, to stop the multiplication of virus within the cells, through which M pro was involved in the release of polypeptides which are functional extensive proteolysis and cleavage of the enzyme itself from the sites of genome, pp1a and ppa1ab . cache = ./cache/cord-270123-m8utyd1m.txt txt = ./txt/cord-270123-m8utyd1m.txt === reduce.pl bib === id = cord-273372-69rlh9or author = Litterman, Nadia title = Small molecules with antiviral activity against the Ebola virus date = 2015-02-09 pages = extension = .txt mime = text/plain words = 3257 sentences = 157 flesch = 48 summary = In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. We have found that indeed there is much prior knowledge regarding small molecules that have been shown to be active against the Ebola virus in vitro or in animal models 10-13 , including a number of FDA-approved drugs 14-16 . Medicinal chemistry analysis of small molecules active against the Ebola virus We have recently described an expert's medicinal chemistry 26 analysis of the over 320 NIH probe compounds using public and commercial sources of chemical structures and the issues related to doing this type of analysis 27 . By organizing the data on small molecules tested against the Ebola virus similarly in a central database and using machine learning models based on public data may help identify additional compounds for testing. cache = ./cache/cord-273372-69rlh9or.txt txt = ./txt/cord-273372-69rlh9or.txt === reduce.pl bib === id = cord-283128-9mbi75de author = Singh, Ramendra K. title = Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid date = 2009-12-09 pages = extension = .txt mime = text/plain words = 4164 sentences = 211 flesch = 57 summary = The resulting product, dissolved in anhydrous pyridine, was added dropwise to the activated folate 5 in 1:1 molar proportion in the presence of DCC and DMAP to yield the compound 10 in 26% (Scheme 4). The molecules 2, 3, 4, 6 and 8 have shown remarkable antibacterial activities with MIC ranging between 0.09 and 0.67 mM (in vitro) against gram-positive cocci (Streptococcus virudans) as well as gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Proteus mirabeilis) bacterial strains. The compound 7, dissolved in dry pyridine (5 ml), was added dropwise to the activated folate ester 5 (286 mg, 0.51 mmol) and stirred the reaction mixture for 15 min. Compound 9 (100 mg, 0.24 mmol), dissolved in dry pyridine (6 ml), was added dropwise to the activated ester 5 (157 mg, 0.28 mmol), stirred the reaction mixture for 20 min and TEA (0.5 ml), DCC (123 mg, 0.6 mmol) and DMAP (32 mg) were further added. cache = ./cache/cord-283128-9mbi75de.txt txt = ./txt/cord-283128-9mbi75de.txt === reduce.pl bib === id = cord-277802-f8pyn3rx author = Roman, Gheorghe title = Mannich bases in medicinal chemistry and drug design date = 2015-01-07 pages = extension = .txt mime = text/plain words = 53972 sentences = 2237 flesch = 41 summary = Aminomethylated derivatives of hydroxycarbazoles have been also mentioned in a different study [60] , which described the synthesis of a small series of phenolic Mannich bases 47 (Fig. 8 ) obtained from 5-substituted 2-hydroxy-5H-benzo[b]carbazole-6,11-diones along with their in vitro anticancer evaluation at National Cancer Institute (NCI) using an in-house developed screening panel of approximately 60 cell lines derived from nine different types of cancer. Recently, Mannich bases 132 ( Fig. 24 ) obtained using Schiff bases derived from 5-fluoroisatin and 4-arylideneaminoanilines as substrates and ciprofloxacin as amine reagent were shown to be generally less potent antibacterials than reference drug ciprofloxacin, although some candidates had MIC values comparable to those of ciprofloxacin against the investigated bacteria [164] . Both types of Mannich bases 133l and 134l, featuring a 1,2,4-triazole moiety at position 5 of the triazolethione scaffold, showed good antibacterial activity, but compounds 134l were generally more potent than 133l, and two of candidates 134l actually had MIC values comparable to those of reference drug ciprofloxacin [177] . cache = ./cache/cord-277802-f8pyn3rx.txt txt = ./txt/cord-277802-f8pyn3rx.txt === reduce.pl bib === id = cord-290539-8ak2tths author = Cagno, Valeria title = Novel broad spectrum virucidal molecules against enveloped viruses date = 2018-12-07 pages = extension = .txt mime = text/plain words = 5524 sentences = 276 flesch = 51 summary = To further elucidate the mechanism of action we performed a virucidal assay in which 9d was incubated with the virus at 10 μM 5μM or 1μM concentration for different times (Fig 6A) or for 1h with serial dilutions of compound ( Fig 6B) ; subsequently, the mixture was titrated on cells and the viral titer was evaluated at dilutions at which the compound concentration was known not to be active in plaquing efficiency assays. The irreversibility of the mechanism was also tested with an assay in which the compound was incubated with the virus for 1h and subsequently the mixture has been diluted in drug free medium for additional 1, 2, 3 or 4 hours before the addition on cells (S2 Fig) . cache = ./cache/cord-290539-8ak2tths.txt txt = ./txt/cord-290539-8ak2tths.txt === reduce.pl bib === id = cord-283301-adjjkqt2 author = Awolade, Paul title = Therapeutic significance of β-glucuronidase activity and its inhibitors: A review date = 2020-02-01 pages = extension = .txt mime = text/plain words = 18960 sentences = 1000 flesch = 38 summary = Based on the foregoing, we extrapolate that the development of potent, specific and non-cytotoxic inhibitors of bGLU is imperative to improving the clinical efficacy of therapeutic agents and effective disease management while bearing in mind the physiological significance of both human and bacterial orthologs of the glycosyl hydrolase. Considering the proven and encouraging potentials of enzyme inhibition and molecular target therapy in drug development, and in continuation of our exploits and expositions thereon [54e58], herein we present a comprehensive review of research undertakings in the present millennium (2000e2019) directed towards the development of potent inhibitors of bGLU that are either natural products or synthetic scaffolds. In a study which examined the protective effects of thymol (54, Fig. 9 ) on inflammation in isoproterenol-induced myocardial infarction using male albino Wistar rats [167] , the therapeutic benefit of inhibiting the release of bGLU, other lysosomal enzymes and pro-inflammatory cytokines was evident in the restoration of near-normal myocardial histology and function, compared to diseased controls. cache = ./cache/cord-283301-adjjkqt2.txt txt = ./txt/cord-283301-adjjkqt2.txt === reduce.pl bib === id = cord-292380-ulsejzqt author = Iwanejko, Jakub title = Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells date = 2020-05-22 pages = extension = .txt mime = text/plain words = 6156 sentences = 349 flesch = 52 summary = Bearing in mind the remarkable precedents of improving the efficacy of cytotoxicity against cancer cell lines by insertion of aminophosphonate moiety and the results of our previous research, we directed our examinations toward the evaluation of antiproliferative properties of the phosphonic derivatives of octahydroquinoxalin-2(1H)-one. Bearing in mind the remarkable precedents of improving the efficacy of cytotoxicity against cancer cell lines by insertion of aminophosphonate moiety and the results of our previous research, we directed our examinations toward the evaluation of antiproliferative properties of the phosphonic derivatives of octahydroquinoxalin-2(1H)-one. Afterwards, wells were washed five times with water and 50 µL of 0.4% solution of SRB (sulforhodamine B, Sigma-Aldrich Chemie GmbH, Steinheim, Germany) in 1% acetic acid (POCh, Gliwice, Poland) was added to each well and plates were again incubated at RT for 30 min. The unbound dye was removed by washing plates five times with 1% acetic acid, while stained cells were treated with 10 mM TRIS (Tris base, Sigma-Aldrich, Chemie GmbH, Steinheim, Germany). cache = ./cache/cord-292380-ulsejzqt.txt txt = ./txt/cord-292380-ulsejzqt.txt === reduce.pl bib === id = cord-293867-c4wnr5xe author = Gürsoy, Elif title = Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents date = 2019-12-06 pages = extension = .txt mime = text/plain words = 2974 sentences = 156 flesch = 50 summary = Besides the wide biological activity spectrum of imidazo[2,1-b] thiazole derivatives, also the compounds bearing hydrazide, acyl-hydrazone and spirothiazolidinone moiety, have been reported in the literature with their various effects such as antibacterial [21] , antifungal [22] , antitubercular [23] , antiviral [24] , anticonvulsant [25] and antidepressant [26] . In this study, we further explored the scaffold containing the imidazo [2,1-b] thiazole ring as the aromatic moiety, that is linked by an amide to a spirothiazolidinone ring system as the aliphatic cyclic moiety and from this point forward, novel derivatives were synthesized (Table 1) , and broadly evaluated for their antiviral and antimycobacterial activity (Fig. 2) . General procedure for the synthesis of 6-(4-bromophenyl)-N 2 -(substituted/non-substituted cycloalkylidene)imidazo[2,1-b]thiazole-3-acetohydrazides (4a-d) 0,005 mol of 3 was boiled in a water bath under reflux with 30 mL of ethanol until a clear solution was obtained. cache = ./cache/cord-293867-c4wnr5xe.txt txt = ./txt/cord-293867-c4wnr5xe.txt === reduce.pl bib === id = cord-296560-ehrww6uu author = Bender, Andreas title = Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR date = 2006-11-07 pages = extension = .txt mime = text/plain words = 10156 sentences = 417 flesch = 40 summary = This chapter discusses recent developments in some of the areas that exploit the molecular similarity principle, novel approaches to capture molecular properties by the use of novel descriptors, focuses on a crucial aspect of computational models—their validity, and discusses additional ways to examine data available, such as those from high-throughput screening (HTS) campaigns and to gain more knowledge from this data. The chapter also presents some of the recent applications of methods discussed focusing on the successes of virtual screening applications, database clustering and comparisons (such as drugand in-house-likeness), and the recent large-scale validations of docking and scoring programs. (Note that this has at the same time been shown empirically in virtual screening experiments [42, 43] .) Some of the methods, namely mutual information and genetic programing, have also been evaluated separately for their use in QSAR studies [44] with respect to a dataset which showed some (typical) problems present in the area, such as a very different sizes of 'active' vs. cache = ./cache/cord-296560-ehrww6uu.txt txt = ./txt/cord-296560-ehrww6uu.txt === reduce.pl bib === id = cord-296970-5yc6u5t3 author = Donmez, Ataberk title = iBioProVis: interactive visualization and analysis of compound bioactivity space date = 2020-08-15 pages = extension = .txt mime = text/plain words = 2216 sentences = 131 flesch = 52 summary = The sources of the set of compounds are not restricted; the compounds may be coming from a list of user-defined compounds indicated as canonical SMILES strings (e.g. the source of this list can be the output of a machine learning method, which predicts interacting compounds to the target of interest), drugs from DrugBank or target proteins' active compounds that are extracted from a reliable compound-target bioactivity measurement dataset, which is a carefully processed and filtered subset of the ChEMBL (v25) database. We also provide a reliable compound-target bioactivity measurement dataset, which is a carefully processed and filtered subset of ChEMBL (v25) database, to be used with iBioProVis. iBioProVis is an interactive web-based visualization tool and it has advantages when compared with existing studies and tools. cache = ./cache/cord-296970-5yc6u5t3.txt txt = ./txt/cord-296970-5yc6u5t3.txt === reduce.pl bib === id = cord-300574-nclkfw4h author = Donno, Dario title = Chapter 9 Nutraceuticals in Alternative and Underutilized Fruits as Functional Food Ingredients: Ancient Species for New Health Needs date = 2018-12-31 pages = extension = .txt mime = text/plain words = 7915 sentences = 369 flesch = 38 summary = Wild plant species are of interest to the food industry because of their ability to replace synthetic chemicals and nutraceuticals; however, the nutritional, economical, and sociocultural values of some neglected and underutilized natural resources have not yet been fully exploited. Some of these less well-known and underutilized fruits, which have the potential to provide novel sources of health-promoting agents, are presented in this chapter (i.e., Asimina triloba (L.) Dunal, Crataegus azarolus L., Lycium barbarum L., Morus nigra L., and Amelanchier canadensis (L.) Medicus). A diet containing high levels of fruits and vegetables has been associated with a lower risk of chronic diseases because, in addition to their high vitamin and mineral content, these foods also contain compounds with health-protective effects, in particular antioxidant and antiinflammatory compounds (Donno et al., 2013b) . Mulberries are sweet fruits and they play an important role in the food industry due to their high levels of bioactive compounds (mulberry fruits can vary in terms of their chemical composition and antioxidant properties). cache = ./cache/cord-300574-nclkfw4h.txt txt = ./txt/cord-300574-nclkfw4h.txt === reduce.pl bib === id = cord-315193-z6v6s46n author = Adhikari, Nilanjan title = Structural Insight Into the Viral 3C-Like Protease Inhibitors: Comparative SAR/QSAR Approaches date = 2017-07-14 pages = extension = .txt mime = text/plain words = 9954 sentences = 585 flesch = 59 summary = In the present report, quantitative structure-activity relationships (QSARs) techniques have been explored to understand the relation between the SARS-CoV 3CL pro and HRV 3C pro enzyme inhibitory activity with the physicochemical and structural properties of these inhibitors developed till now. (2008) reported some cinanserin analogs as SARS-CoV 3CL pro inhibitors (Table 11 .18), for which the QSAR model obtained was as shown by Eq. (2013b) reported a series of dipeptide-type SARS-CoV 3CL protease inhibitors (Table 11 .27) whose activity was shown to be controlled by the molar refractivity (CMR) and the polar volume (Pol Vol) of the compounds [Eq. QSAR models exhibited that the physicochemical parameters, such as dipole moment, PSA, polar volume, hydrophobicity, molar refractivity, SA, and molecular volume of the compounds play a crucial role in controlling both SARS-CoV 3CL pro and HRV 3C pro inhibitory activities. cache = ./cache/cord-315193-z6v6s46n.txt txt = ./txt/cord-315193-z6v6s46n.txt === reduce.pl bib === id = cord-300872-blycbi4u author = Saadeh, Haythem A. title = Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines date = 2020-09-21 pages = extension = .txt mime = text/plain words = 16077 sentences = 768 flesch = 44 summary = Some of these strains have even become resistant to many antibiotics and chemotherapeutic agents; These prepared compounds were subjected to bioactivity screening against the highly pathogenic H5N1 avian influenza viruses, with the results expressed as percentages of growth inhibition, and to cytotoxicity evaluation against the A549 cell line. A synthetic procedure (Scheme 13) involved a condensation reaction between the amino group (NH2) in 49 and the carbonyl group in salicylic aldehyde (50), followed by intramolecular cyclization under a These prepared compounds were screened for potential anticancer activity against MCF-7, HCT 116, HepG-2, and A549 using the MMT assay. This compound was screened against MCF-7 and Hela cancer cell lines using MMT assay, giving IC50 values of 21.02 and 27.73 mM, respectively In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives (Scheme 14) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [36] . cache = ./cache/cord-300872-blycbi4u.txt txt = ./txt/cord-300872-blycbi4u.txt === reduce.pl bib === id = cord-309052-3h0g7s9v author = Alam, Fiaz title = Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review date = 2017-12-15 pages = extension = .txt mime = text/plain words = 9659 sentences = 569 flesch = 46 summary = The Lymphangiogenesis inhibition (Jeong et al., 2013) Anti-Alzheimer (Chen et al., 2013) Carboxylesterase inhibitors 33 Isobavachin Flavonoid Seed/fruit Osteoblast (Li et al., 2014) 34 Isopsoralen Furanocoumarin Whole plant Antiprotozoal 35 Neobavaisoflavone Seeds Antibacterial (Khatune et al., 2004) 36 Psoralen Furanocoumarin Whole plant/root Leucoderma, psoriasis Anticancer (Hao et al., 2014) , antioxidant , anti-Alzheimer (Somani et al., 2015) , Collagengenesis 37 Psoralidin Coumarin Whole plant/seed Estrogen receptor modulator (Liu et al., 2014; Lim et al., 2011) Antioxidant (Wang, Yin, Zhang, Peng, & Kang, 2013b) , antibacterial (Khatune et al., 2004) Anti-diabetic (Behloul & Wu, 2013) , antiprotozoal Anticancer (Hao et al., 2014; Limper et al., 2013; Yang et al., 1996) , anti-depressent (Farahani et al., 2015) 38 Psoracorylifol D Flavonoid Seed Lymphangiogenesis inhibition (Jeong et al., 2013) Psoracoumestan Coumestans Seeds essential oil Anti-cancer (Limper et al., 2013) 39 Xanthoangelol Chalcone Seeds Anticancer (Limper et al., 2013) FIGURE 2 Structures of important compounds isolated from Psoralea corylifolia psoralester is a 10-membered lactone compound and the latter is an isomer of already known compound bayachromene (Tewari & Bhakuni, 2010) . cache = ./cache/cord-309052-3h0g7s9v.txt txt = ./txt/cord-309052-3h0g7s9v.txt === reduce.pl bib === id = cord-306934-29ljbl7g author = Tonelli, Michele title = Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date = 2009-07-01 pages = extension = .txt mime = text/plain words = 8526 sentences = 442 flesch = 58 summary = Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. First of all, the binding site identified by our procedure is very close to the putative binding site proposed for two allosteric inhibitors of BVDV RdRp, VP32947 and BPIP, 23 Table 5 Cytotoxicity against MT-4, MDBK, BHK and Vero-76 cell lines and YFV, Reo-1, CVB-2, RSV, HSV-1 and Sb-1 inhibitory activity of triazene derivatives of structure F and G Tables 3 and 4. In view of these considerations, molecular modeling investigations were performed to study wether the active compounds of structures A-C could target the BVDV RNA-dependent RNA-polymerase (RdRp), which shares some structural similarity with HCV RdRp. Indeed a good agreement was observed between the trend exhibited by the IC 50 (calculated from the estimated free energies of binding) and the corresponding biological activities determined for these compounds in BVDV infected MDBK cell line. cache = ./cache/cord-306934-29ljbl7g.txt txt = ./txt/cord-306934-29ljbl7g.txt === reduce.pl bib === id = cord-301349-m4nr3pqx author = Mirza, Muhammad Usman title = Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach date = 2020-09-02 pages = extension = .txt mime = text/plain words = 7369 sentences = 370 flesch = 46 summary = The aim of this study was to discover selective CCR5, CXCR4 and dual CCR5/CXCR4 antagonists based on both receptor-and ligand-based virtual screening methods together with molecular dynamics (MD) simulations and binding free energy calculations. The most promising compounds resulting from VS were evaluated for antiviral activity by a luciferase assay in TZM-bl cells infected with wild type HIV-1 strains NL4.3 (CXCR4-tropic strain, X4) and BaL (CCR5-tropic strain, R5). After a careful post-MD inspection, 43 compounds were selected based on the following criteria; (1) overall backbone stability of the protein/ligand complex, (2) electrostatic (ΔE ele ) and van der Waals (ΔE vdw ) interaction energy, (3) H-bonds occupancy, and (4) binding pocket residual contribution towards ligands. Compound 27, the most promising compound after receptor-based screening (IC 50 = 10.64 µM), showed a significant H-bond interaction profile with the residues lining the binding pocket of CCR5, as reported also for maraviroc [39, 80] . cache = ./cache/cord-301349-m4nr3pqx.txt txt = ./txt/cord-301349-m4nr3pqx.txt === reduce.pl bib === id = cord-317628-1inxq7t5 author = Cuccarese, Michael F. title = Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date = 2020-08-14 pages = extension = .txt mime = text/plain words = 9573 sentences = 487 flesch = 43 summary = We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). cache = ./cache/cord-317628-1inxq7t5.txt txt = ./txt/cord-317628-1inxq7t5.txt === reduce.pl bib === id = cord-318854-xaus3bma author = Sun, Yi title = Chapter 4 Bioactivity and Synthesis of Diarylheptanoids From Alpinia officinarum date = 2016-12-31 pages = extension = .txt mime = text/plain words = 5322 sentences = 298 flesch = 48 summary = In this review, we discuss the antitumor-promoting, antiinflammatory, cytotoxic, antimicrobial, antiinfluenza, and antiherpes simplex-1 virus activities of diarylheptanoids isolated from galangal resulting from our own and other research groups' investigation. Compound 6 showed the strongest activity among the four diarylheptanoids (IC 50 : 10 μM), and it also inhibited the mRNA expression of tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2, as well as protein levels of microphthalmia-associated transcription factor (MITF) [52] . Compounds 2, 6, 15, 16, 47, and 48 were tested for their inhibitory effects on NO production in the LPS-activated macrophage cell line RAW 264.7 [15] . Thus, the reports cited above suggest that diarylheptanoids possess inhibitory effects against inflammatory and tumor-promoting activities. Compound 4 was also active against influenza virus with an EC 50 value of <10 μg/mL [61] , which suggests that 4 is an effective diarylheptanoid against both RSV and influenza virus in vitro. cache = ./cache/cord-318854-xaus3bma.txt txt = ./txt/cord-318854-xaus3bma.txt === reduce.pl bib === id = cord-320591-re99v1qt author = Le, Thanh Ninh title = Bioactive Compounds and Bioactivities of Brassica oleracea L. var. Italica Sprouts and Microgreens: An Updated Overview from a Nutraceutical Perspective date = 2020-07-27 pages = extension = .txt mime = text/plain words = 8182 sentences = 395 flesch = 34 summary = Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). In summary, previous studies showed that broccoli sprout extracts rich in vitamins, carotenoids, and phenolic compounds showed very high antioxidant activity in both in vitro and in vivo tests (Table 4) . Moreover, the previous studies have focused on several biological activities of broccoli seedlings, such as antioxidant, anticancer, antimicrobial, and anti-inflammatory, as well as the potentially beneficial effects for patients with cancers, diabetes, and obesity. cache = ./cache/cord-320591-re99v1qt.txt txt = ./txt/cord-320591-re99v1qt.txt === reduce.pl bib === id = cord-323479-vlgv3nwq author = Speranza, Jasmine title = Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies date = 2020-03-01 pages = extension = .txt mime = text/plain words = 14357 sentences = 712 flesch = 42 summary = tinctoria has been thoroughly investigated and the plant was proven to contain many valuable biologically active compounds, including several alkaloids, among which tryptanthrin, indirubin, indolinone, phenolic compounds, and polysaccharides as well as glucosinolates, carotenoids, volatile constituents, and fatty acids. In the lyophilized extracts' analysis, beyond the characterization and quantification of 122 compounds previously described, the following indole derivatives were described for the first time: acetylindican, malonylindican, two Another important compound of this class is tryptanthrin, indolo-[2,1-b]-quinazoline alkaloid ( Figure 4 ), which is also responsible for some biological activities of I. In particular, the study concerned the evaluation of anti-microbial activity of fractions obtained from different parts of the plant (branches, flowers, leaves, and roots) by extraction with 14 different solvents, which was performed using a micro-titer plate method against seven bacterial and four fungal strains. Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin cache = ./cache/cord-323479-vlgv3nwq.txt txt = ./txt/cord-323479-vlgv3nwq.txt === reduce.pl bib === id = cord-323093-u3ozc9ry author = Rathnayake, Athri D. title = 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date = 2020-08-19 pages = extension = .txt mime = text/plain words = 7158 sentences = 362 flesch = 56 summary = After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection. cache = ./cache/cord-323093-u3ozc9ry.txt txt = ./txt/cord-323093-u3ozc9ry.txt === reduce.pl bib === id = cord-327946-mqakaisa author = Massari, Serena title = Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase date = 2020-10-16 pages = extension = .txt mime = text/plain words = 3467 sentences = 205 flesch = 48 summary = title: Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide scaffolds. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. Finally, with the aim to gain information on how two different moieties, such as the cHTC and the 2-carbamoylphenyl, showed a favorable ability to disrupt PA-PB1 interaction, computational studies were performed to predict the binding mode of benzamide derivative 23 within the PA cavity with respect to hit compound 4. cache = ./cache/cord-327946-mqakaisa.txt txt = ./txt/cord-327946-mqakaisa.txt === reduce.pl bib === id = cord-326922-bajpr5a2 author = Watson, C. James title = Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors date = 2020-11-02 pages = extension = .txt mime = text/plain words = 7095 sentences = 417 flesch = 38 summary = In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA's Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] . cache = ./cache/cord-326922-bajpr5a2.txt txt = ./txt/cord-326922-bajpr5a2.txt === reduce.pl bib === id = cord-328176-fck2ktxi author = Mahapatra, Manojkumar title = Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity date = 2013-02-19 pages = extension = .txt mime = text/plain words = 2398 sentences = 140 flesch = 46 summary = This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC(50) value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation. It is interesting to note that preferably compounds with tridentate ligand characteristics (IIl, IIi, and IIc) showed potent anti-proliferative activity against the HL60 cells (Table 3 ). The compounds investigated are known as intermediates in the synthesis of many thiosemicarbazones but their usefulness as medicinally active agents has not yet been studied. cache = ./cache/cord-328176-fck2ktxi.txt txt = ./txt/cord-328176-fck2ktxi.txt === reduce.pl bib === id = cord-328834-yetnlb2j author = Mohsin, Noor ul Amin title = Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review date = 2020-06-15 pages = extension = .txt mime = text/plain words = 5675 sentences = 458 flesch = 57 summary = Upon in vitro evaluation, compound 10 ( Fig. 3) showed prominent activity (87% growth inhibition) against colon cancer cell line (HCT-116) as compared to fluorouracil (67% inhibition). Derivatives bearing electron withdrawing groups at positions # 5, # 6 and # 7 of chromone scaffold showed better activity. Upon evaluation as anticancer agents by MTT assay, compounds 22 (IC 50 = 1.42 ± 0.13 mM) and 23 (IC 50 = 2.92 ± 0.94 mM) showed prominent in vitro activity versus breast cancer cell line (T47D) as compared to doxorubicin (IC 50 = 0.33 ± 0.05 mM). Incorporation of methyl and ethyl group in the heterocyclic ring showed comparable activity to unsubstituted derivatives [47] . Attachment of methyl group with chromone core also produced less active derivatives [51] . synthesized fluorine-containing chromone and tetrazole hybrid molecules by Ugi-azide reaction [63] These derivatives displayed moderate antimicrobial activity as is evident by compound 51 (MIC = 20 mg/mL) activity versus Pseudomonas aeruginosa (P. cache = ./cache/cord-328834-yetnlb2j.txt txt = ./txt/cord-328834-yetnlb2j.txt === reduce.pl bib === id = cord-328962-1c4vqaqr author = Benítez-Cardoza, Claudia Guadalupe title = Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug date = 2020-06-15 pages = extension = .txt mime = text/plain words = 3344 sentences = 184 flesch = 54 summary = KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. We use the amino acids reported in the crystallographic structure of the interaction between the S-protein-RBD of SARS-CoV-2 and ACE2 (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353 and Arg357 in ACE2) [10] [22] , therefore, using the crystallographic structure of ACE2 (PDB 1R42), we carried out a Docking directed to these mentioned residues using a library of compounds (EXPRESS-pick Collection from Chembridge Corp.) to select the best compounds, and that these can affect the interaction between ACE2 and SARS-CoV-2, making these results an important contribution to establishing the foundations that allow the development of a drug that optimizes the resolution of this pandemic. cache = ./cache/cord-328962-1c4vqaqr.txt txt = ./txt/cord-328962-1c4vqaqr.txt === reduce.pl bib === id = cord-329078-gnnis7pl author = Musella, Simona title = Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor date = 2016-11-29 pages = extension = .txt mime = text/plain words = 3935 sentences = 215 flesch = 48 summary = title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor Tryptamine derivative 17a was found to have a selective inhibitory activity against human varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. Arbidol [34] and delavirdine [35] , are examples of marketed indole-containing antiviral drugs, whereas Panobinostat (LBH589) [36] , being a HDAC (histone deacetylase) inhibitor, is actively undergoing clinical evaluation against human immunodeficiency virus (HIV) type 1 (See Fig. 1 ). The antiviral activity was expressed as EC50, being the compound concentration required to reduce virus-plaque formation (VZV) by 50%. The mixture was stirred for 3 h at room temperature, then was washed with water (3 Â 50 mL), dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using DCM/MeOH (9:1 v/v) as mobile phase. 4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus cache = ./cache/cord-329078-gnnis7pl.txt txt = ./txt/cord-329078-gnnis7pl.txt === reduce.pl bib === id = cord-338436-0z828org author = Tzou, Philip L. title = Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date = 2020-09-09 pages = extension = .txt mime = text/plain words = 8193 sentences = 522 flesch = 46 summary = Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. cache = ./cache/cord-338436-0z828org.txt txt = ./txt/cord-338436-0z828org.txt === reduce.pl bib === id = cord-330465-16j5vm7h author = Marciniec, Krzysztof title = Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study date = 2020-08-05 pages = extension = .txt mime = text/plain words = 6908 sentences = 396 flesch = 48 summary = The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC(50) (half maximal inhibitory concentration) equal to 0.02 μM. In order to check the potential toxic properties of the compounds 3-5, docking study of phosphate betulin derivatives to cellular proteins was carried out. According to the results of docking (Table S1 ) obtained from AutoDock Vina, four potential SARS-CoV-2 inhibitors (BVM, betulinic acid, and compounds 4 and 6) were selected based on a lower negative dock energy value. cache = ./cache/cord-330465-16j5vm7h.txt txt = ./txt/cord-330465-16j5vm7h.txt === reduce.pl bib === id = cord-333675-vkk2frnf author = Hamada, Manabu title = Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides date = 2013-07-04 pages = extension = .txt mime = text/plain words = 4256 sentences = 234 flesch = 56 summary = A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. N 1crotyl-1,2,4-triazole-3-bis-Boc-carboxamide 19 was then subjected to the olefin cross metathesis reaction, with bis(POM)-allylphosphonate in CH 2 Cl 2 to obtain the desired compound 20 in 16% yield. The title bis(POM) (E)-4-phosphono-but-2-en-1-yl acyclic nucleosides were subjected to an in vitro antiviral screening using a wide spectrum of viruses, in MDKC cell cultures for anti-influenza virus activity, in Vero cell cultures for an antiviral activity against Para-influenza3 shown) only compound 31 showed activity at an EC 50 of w10 mM (AD-169 strain) with no observed cytotoxicity at 100 mM ( Table 2) . cache = ./cache/cord-333675-vkk2frnf.txt txt = ./txt/cord-333675-vkk2frnf.txt === reduce.pl bib === id = cord-336759-cu1uprwm author = Cihan-Üstündağ, Gökçe title = Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives date = 2019-07-17 pages = extension = .txt mime = text/plain words = 2993 sentences = 183 flesch = 55 summary = Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Based on these insights and our objective to optimize the antimicrobial activity of indolyl thiazolidinones and spirothiazolidinones, we here report the chemical synthesis, structural characterization and in vitro antitubercular, antiviral, antibacterial, and antifungal evaluation of new 5-chloro-3-phenyl-N(2,7,8,9substituted/nonsubstituted-3-oxo-1-thia-4-azaspiro [4.4] nonan/ [4.5] decan-4-yl)-1H-indole-2-carboxamides 4a-4i, 5a-5h (Fig. 1e ). As shown in Table 1 , compounds 4 h and 5h, bearing a phenyl substituent at position 8 of the spiro ring, exhibited the highest anti-TB activity at concentrations of 3.9 and 7.8 µM, respectively. The broad antibacterial and antifungal activity of compounds 4a-4i and 5a-5 h was further assessed using The experiment was performed twice and the same results were obtained a MIC, the actual minimum inhibitory concentration required to inhibit the growth of 100% of organisms cache = ./cache/cord-336759-cu1uprwm.txt txt = ./txt/cord-336759-cu1uprwm.txt === reduce.pl bib === id = cord-330994-6nu7utu1 author = Abdelrheem, Doaa A. title = The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation date = 2020-10-01 pages = extension = .txt mime = text/plain words = 5306 sentences = 323 flesch = 48 summary = title: The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. [6] So, we study the inhibitory effect of some bioactive compounds obtained from natural sources against SARS-CoV-2-3CLpro and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT). The crystal structures of SARS-CoV-2-3CLpro (PDB code: 6LU7) and main proteases of SARS-Coronavirus (Mpro) with (PDB IDs: 2GTB and 3TNT) were downloaded from the Protein Data Bank (www.pdb.org), and any heteroatoms and water molecules were removed before molecular docking studies. Based on our molecular docking analysis we found that among all studied compounds, caulerpin has the highest binding affinity against all studied receptors 6LU7, 3TNT, and 2GTB with compared to some proposed antiviral drug currently used in COVID-19 treatment. cache = ./cache/cord-330994-6nu7utu1.txt txt = ./txt/cord-330994-6nu7utu1.txt === reduce.pl bib === id = cord-344598-5drr3fyt author = Khanna, Leena title = Spiro‐Indole‐Coumarin Hybrids: Synthesis, ADME, DFT, NBO Studies and In Silico Screening through Molecular Docking on DNA G‐Quadruplex date = 2020-03-19 pages = extension = .txt mime = text/plain words = 3901 sentences = 264 flesch = 56 summary = Thus, in the present study, the biological importance of 22 compounds including six new spiro indole-coumarin hybrids as DNA quadruplex groove binders has been evaluated by performing molecular docking studies on DNA G-quadruplexes of the human genome. Finally, Density Functional Theory (DFT) calculations, NBO analysis, and MEP plots are drawn for hybrids to prove their chemical reactivity and stability. 1 H NMR spectrum showed the presence of methylene of thiazolidine as two doublets at δ 4.37 and δ 4.05 besides the usual aromatic protons of indole, indazole and coumarin moieties. Table 1 also shows all six newly synthesized spiro indolecoumarin hybrids 10 a-c and 12 a-c are having high binding energy as compared to intermediary Schiff bases, isatin, their non-hybrid counterparts and the reference compounds. Binding interaction of about 22 compounds including these hybrids with DNA G-quadruplex of the human genome, was screened using Molecular docking studies. cache = ./cache/cord-344598-5drr3fyt.txt txt = ./txt/cord-344598-5drr3fyt.txt === reduce.pl bib === id = cord-347547-makm0j09 author = Duran-Frigola, Miquel title = Bioactivity Profile Similarities to Expand the Repertoire of COVID-19 Drugs date = 2020-07-16 pages = extension = .txt mime = text/plain words = 1942 sentences = 99 flesch = 46 summary = By comparing the set of drugs reported to be potentially active against SARS-CoV-2 to a universe of 1 million bioactive molecules, we identify compounds that display analogous chemical and functional features to the current COVID-19 candidates. Searches can be filtered by level of evidence and mechanism of action, and results can be restricted to drug molecules or include the much broader space of bioactive compounds. Indeed, we conducted a limited review of the most relevant scientific literature and identified over 200 compounds that are potentially active against COVID-19 with different levels of experimental support, from purely computational predictions to preclinical and drugs already in clinical trials. We use the list of COVID-19 compounds extracted from the literature, with different levels of experimental evidence, as bait to search for compounds with similar bioactivity or chemical features among the 800,000 molecules contained in the CC. cache = ./cache/cord-347547-makm0j09.txt txt = ./txt/cord-347547-makm0j09.txt === reduce.pl bib === id = cord-340832-412qre64 author = Liang, Pi‐Hui title = Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis date = 2006-01-05 pages = extension = .txt mime = text/plain words = 3832 sentences = 221 flesch = 55 summary = In the screening for 166 www.chembiochem.org a-glucosidase (bakers' yeast) inhibition, about two-thirds of reaction products were found to be more potent than 4 (see Supporting Information for overall library inhibitory activities). With the potent a-glucosidase inhibitors in hand, we tested their potential antiviral effect based on our previous assay system for JEV and DEN-2. [16] The weaker a-glucosidase inhibitors 39-41, derived from core 4 with eight to ten carbons (Scheme 3), were then evaluated, and we found that 39-41 at 10 or 50 mM did not inhibit either JEV or DEN-2 infection (data not shown) in the cell-based assay. The N-alkylated derivatives of compound 24 were also tested for antiviral activity, and 36-38, which contain lipophilic alkyl groups, were the most active, with an IC 50 of about 5-10 mM against JEV, DEN-2, and SARS-CoV infection. However, extending the alkyl chain at the ring nitrogen gave the most potent human b-hexosaminidase inhibitor known to date, that is, compound 54, with a K i value of 2.6 nM. cache = ./cache/cord-340832-412qre64.txt txt = ./txt/cord-340832-412qre64.txt === reduce.pl bib === id = cord-340331-51yq1rdo author = Tonelli, Michele title = Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus date = 2017-07-28 pages = extension = .txt mime = text/plain words = 6160 sentences = 285 flesch = 42 summary = We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. The compounds, object of the present study, are characterized by the 1-aryl-4,6-diamino-1,2-dihydrotriazine scaffold, such as the cited cycloguanil, which was identified by us as prototype (1) of a new class of antiviral agents exploiting a host DHFR inhibition mechanism. Since host cell DHFR inhibition seemed the plausible explanation for the observed antiviral effect, we performed a combination experiment in which RSV-infected HeLa cells were exposed to compound 14 in combination with different concentrations of the natural DHFR substrate dihydrofolic acid ( reaction has a much higher impact on virus replication than on cell growth, which concurs with the promising antiviral selectivity of our host-directed DHFR inhibitors. The interesting dual activity of the 1-aryl-4,6-diamino-1,2dihydrotriazines against influenza and respiratory syncytial viruses, via inhibition of the cellular (human) DHFR enzyme, points to this host factor as a new therapeutic target for these two respiratory viruses. cache = ./cache/cord-340331-51yq1rdo.txt txt = ./txt/cord-340331-51yq1rdo.txt === reduce.pl bib === id = cord-345750-dk1exw9l author = Kulikov, A. S. title = Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans date = 2014-01-07 pages = extension = .txt mime = text/plain words = 2274 sentences = 188 flesch = 67 summary = All target compounds were evaluated for both antimitotic microtubule destabilizing effect in a phenotypic sea urchin embryo assay and cytotoxicity in a panel of 60 human cancer cell lines. Water soluble biologically active compounds contain ing both cycles, e.g., (1,2,3 triazol 1 yl)furazans 1, ex hibiting other mechanisms of action were synthesized. In addition, to extend the scope of triazolylfurazan derivatives with potential antineoplastic activity, we used the Clauson-Kaas pyrrole synthesis involving the reaction of primary amino group of the furazan ring with dimethoxytetra hydrofuran. Therefore, unpurified esters 4a-g were hydrolyzed to the corresponding acids 5a-g, which also without further purification were subsequently thermally decarboxylated to target 3 amino 4 [5 aryl(hetaryl) 1H 1,2,3 triazol 1 yl]furazans 6a-g in high yields. Subsequent Clauson-Kaas condensation of synthesized triazolylfurazans 6 with dimethoxytetrahydrofuran yielded a series of 4 [5 aryl (hetaryl) 1H 1,2,3 triazol 1 yl] (3 pyrrol 1 yl)furazans 7. cache = ./cache/cord-345750-dk1exw9l.txt txt = ./txt/cord-345750-dk1exw9l.txt === reduce.pl bib === id = cord-352844-wggg3ynb author = Annunziata, Francesca title = An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities date = 2020-06-29 pages = extension = .txt mime = text/plain words = 50752 sentences = 2326 flesch = 42 summary = Again, the coumarin derivative showed inhibitory activity on 15-LOX-1 in PC3 and DU145 cell lines, thus inducing apoptosis of the cancer cell, with the same mechanism of The results represent a good starting point for the design of novel derivatives, because most of the examined compounds exhibited selective toxicity on HeLa cells (IC 50 values between 136.4 ± 1.90 µM and 172.2 ± 1.80 µM after 24 h), whereas no negative effects on HDF normal cell's growth was detected. Since tacrine is a well-known inhibitor of the catalytic site of AChE, whereas coumarins showed affinity for the peripheral anionic site (PAS) [161] , this new compounds may be potential dual-and therefore more powerful -inhibitors of ChEs. The in vitro AChE and BuChE inhibitory activity was evaluated using the Ellman's method [159] ; among all the tested molecules, compound 105 resulted the best in AChE inhibition (IC 50 Thanks to their simple structural architecture and chemical stability, coumarins can be easily synthesized and modified in order to produce more active and selective compounds. cache = ./cache/cord-352844-wggg3ynb.txt txt = ./txt/cord-352844-wggg3ynb.txt ===== Reducing email addresses cord-003427-0dddrh4e cord-020010-q58x6xb0 cord-296970-5yc6u5t3 cord-328176-fck2ktxi Creating transaction Updating adr table ===== Reducing keywords cord-000445-2x7dfl1q cord-002237-200ondzx cord-003427-0dddrh4e cord-006139-9063uhox cord-013387-q91052qw cord-003539-tazd6dvm cord-003341-z5w56zeq cord-012773-wtgk2d68 cord-011251-rjyipcfv cord-016425-8yd2bkf1 cord-014863-jyti99xq cord-017041-0zxoq68m cord-021013-xvc791wx cord-021419-nypnib0h cord-023284-i0ecxgus cord-020010-q58x6xb0 cord-024652-4i6kktl0 cord-034363-6uscua0y 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cord-340331-51yq1rdo cord-345750-dk1exw9l cord-352844-wggg3ynb cord-327946-mqakaisa cord-333675-vkk2frnf Creating transaction Updating wrd table ===== Reducing urls Creating transaction Updating url table ===== Reducing named entities cord-002237-200ondzx cord-000445-2x7dfl1q cord-003427-0dddrh4e cord-006139-9063uhox cord-003341-z5w56zeq cord-011251-rjyipcfv cord-013387-q91052qw cord-014863-jyti99xq cord-012773-wtgk2d68 cord-003539-tazd6dvm cord-016425-8yd2bkf1 cord-023584-yaxawqhj cord-025119-201ac32t cord-252108-04xr5xdl cord-017041-0zxoq68m cord-021013-xvc791wx cord-021419-nypnib0h cord-034363-6uscua0y cord-103271-l9n27ocf cord-024652-4i6kktl0 cord-000536-0mn1gbll cord-033493-kslzdy8q cord-023284-i0ecxgus cord-253276-mqcwk2ow cord-254036-0karwgz2 cord-255862-84u3c33m cord-260014-q5sug7uu cord-259744-r9j5yzfc cord-261366-mtcalbo5 cord-261170-arnwk287 cord-273372-69rlh9or cord-020010-q58x6xb0 cord-264316-do0px1gq cord-270123-m8utyd1m cord-283128-9mbi75de cord-290539-8ak2tths cord-283301-adjjkqt2 cord-292380-ulsejzqt cord-293867-c4wnr5xe cord-296560-ehrww6uu cord-296970-5yc6u5t3 cord-300574-nclkfw4h cord-315193-z6v6s46n cord-306934-29ljbl7g cord-317628-1inxq7t5 cord-300872-blycbi4u cord-309052-3h0g7s9v cord-301349-m4nr3pqx cord-318854-xaus3bma cord-326922-bajpr5a2 cord-320591-re99v1qt cord-323479-vlgv3nwq cord-327946-mqakaisa cord-277802-f8pyn3rx cord-323093-u3ozc9ry cord-328176-fck2ktxi cord-328834-yetnlb2j cord-329078-gnnis7pl cord-328962-1c4vqaqr cord-338436-0z828org cord-330465-16j5vm7h cord-333675-vkk2frnf cord-336759-cu1uprwm cord-330994-6nu7utu1 cord-344598-5drr3fyt cord-347547-makm0j09 cord-340832-412qre64 cord-340331-51yq1rdo cord-345750-dk1exw9l cord-352844-wggg3ynb Creating transaction Updating ent table ===== Reducing parts of speech cord-002237-200ondzx cord-003427-0dddrh4e cord-003341-z5w56zeq cord-000445-2x7dfl1q cord-011251-rjyipcfv cord-014863-jyti99xq cord-006139-9063uhox cord-025119-201ac32t cord-252108-04xr5xdl cord-003539-tazd6dvm cord-023584-yaxawqhj cord-033493-kslzdy8q cord-016425-8yd2bkf1 cord-012773-wtgk2d68 cord-013387-q91052qw cord-103271-l9n27ocf cord-034363-6uscua0y cord-000536-0mn1gbll cord-253276-mqcwk2ow cord-254036-0karwgz2 cord-260014-q5sug7uu cord-255862-84u3c33m cord-259744-r9j5yzfc cord-261366-mtcalbo5 cord-017041-0zxoq68m cord-261170-arnwk287 cord-021013-xvc791wx cord-021419-nypnib0h cord-273372-69rlh9or cord-270123-m8utyd1m cord-023284-i0ecxgus cord-283128-9mbi75de cord-290539-8ak2tths cord-292380-ulsejzqt cord-024652-4i6kktl0 cord-264316-do0px1gq cord-296560-ehrww6uu cord-300574-nclkfw4h cord-309052-3h0g7s9v cord-306934-29ljbl7g cord-318854-xaus3bma cord-301349-m4nr3pqx cord-315193-z6v6s46n cord-317628-1inxq7t5 cord-320591-re99v1qt cord-327946-mqakaisa cord-326922-bajpr5a2 cord-328176-fck2ktxi cord-328834-yetnlb2j cord-329078-gnnis7pl cord-328962-1c4vqaqr cord-336759-cu1uprwm cord-333675-vkk2frnf cord-323093-u3ozc9ry cord-347547-makm0j09 cord-340832-412qre64 cord-300872-blycbi4u cord-345750-dk1exw9l cord-330994-6nu7utu1 cord-293867-c4wnr5xe cord-344598-5drr3fyt cord-330465-16j5vm7h cord-296970-5yc6u5t3 cord-340331-51yq1rdo cord-338436-0z828org cord-323479-vlgv3nwq cord-283301-adjjkqt2 cord-020010-q58x6xb0 cord-277802-f8pyn3rx cord-352844-wggg3ynb Creating transaction Updating pos table Building ./etc/reader.txt cord-277802-f8pyn3rx cord-352844-wggg3ynb cord-024652-4i6kktl0 cord-277802-f8pyn3rx cord-020010-q58x6xb0 cord-340331-51yq1rdo number of items: 70 sum of words: 561,911 average size in words: 9,523 average readability score: 48 nouns: compounds; activity; compound; cells; derivatives; virus; cell; inhibitors; drug; inhibition; group; synthesis; bases; acid; studies; structure; results; study; values; treatment; reaction; agents; protein; activities; drugs; effects; series; plant; effect; properties; ring; cancer; data; concentration; inhibitor; receptor; molecules; coumarin; ml; assay; evaluation; presence; disease; model; number; development; groups; infection; growth; type verbs: using; shown; based; compared; inhibit; found; containing; binding; including; obtain; evaluate; giving; reported; tested; exhibit; synthesize; produced; derived; increasing; induced; resulting; follows; led; done; reducing; determine; caused; known; treated; suggesting; identify; observed; developed; isolated; performed; provides; indicated; described; involved; demonstrated; studied; considered; added; substituted; related; selected; presented; calculated; displayed; made adjectives: active; anti; antiviral; new; human; potent; different; molecular; biological; high; novel; inhibitory; viral; potential; several; natural; important; many; antibacterial; effective; clinical; significant; antifungal; similar; various; inflammatory; higher; good; cytotoxic; resistant; low; structural; selective; antimicrobial; small; therapeutic; specific; free; non; positive; recent; secondary; promising; bioactive; first; bacterial; synthetic; aromatic; phenolic; possible adverbs: also; well; respectively; however; highly; therefore; less; recently; previously; even; moreover; significantly; finally; furthermore; often; generally; currently; especially; still; already; usually; first; widely; much; directly; together; particularly; almost; probably; approximately; namely; mainly; biologically; hence; interestingly; relatively; subsequently; rather; similarly; later; far; ns3; indeed; clearly; now; newly; slightly; nevertheless; commonly; structurally pronouns: their; it; we; its; they; our; i; them; itself; us; his; bglu; themselves; one; me; you; he; her; your; nr-818; puc; my; mrnas; he16; 63a; smaller/; ser146; scid; s; ours; o*-orbital; nf279; ligand−protein; jchem; indole-2-carboxamides; ile235; i-[(3'-allyl-2'-hydroxybenzilidene)amino]-3-hydroxyguanidine; hdp-(s)-hpmpa; cord-014863-jyti99xq; chembl1800935; bbg100; 7methylimidazo[1,2-c]pyrimidine; 30e34 proper nouns: Mannich; Fig; SARS; IC; mg; Synthesis; C; N; CoV-2; A; Table; CoV; CH; RNA; HIV; H; P.; D; mL; B; II; HIV-1; USA; EC; M; I.; NMR; HCV; kg; ¼; K; E.; tinctoria; L.; S.; QSAR; ±; corylifolia; University; CCR5; C.; F; Figure; L; IC50; R; MERS; COVID-19; MS; SAR keywords: compound; activity; sars; cell; virus; synthesis; table; scheme; plant; antiviral; inhibitor; effect; derivative; covid-19; study; structure; rna; qsar; product; nmr; model; mic; mers; isolate; hiv-1; hiv; hcv; gram; fungus; food; extract; drug; cov-2; boc; acid; xii; wound; wnv; vzv; virtual; virology; usa; university; tsh; trypanosomal; tnf; tinctoria; thermo; tgf; test one topic; one dimension: compounds file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163371/ titles(s): Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances three topics; one dimension: compounds; activity; compounds file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133865/, https://www.ncbi.nlm.nih.gov/pubmed/25462280/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212785/ titles(s): 19th ICAR Abstracts: | Mannich bases in medicinal chemistry and drug design | Natural Products as Fungicide and Their Role in Crop Protection five topics; three dimensions: compounds activity compound; activity mannich bases; activity compounds compound; activity compounds virus; syn tinctoria compounds file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168536/, https://www.ncbi.nlm.nih.gov/pubmed/25462280/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149660/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133865/, https://doi.org/10.3390/plants9030298 titles(s): Abstracts of publications related to QASR | Mannich bases in medicinal chemistry and drug design | Main trends in the design of semi-synthetic antibiotics of a new generation | 19th ICAR Abstracts: | Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies Type: cord title: keyword-compound-cord date: 2021-05-24 time: 22:41 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:compound ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-330994-6nu7utu1 author: Abdelrheem, Doaa A. title: The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation date: 2020-10-01 words: 5306.0 sentences: 323.0 pages: flesch: 48.0 cache: ./cache/cord-330994-6nu7utu1.txt txt: ./txt/cord-330994-6nu7utu1.txt summary: title: The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. [6] So, we study the inhibitory effect of some bioactive compounds obtained from natural sources against SARS-CoV-2-3CLpro and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT). The crystal structures of SARS-CoV-2-3CLpro (PDB code: 6LU7) and main proteases of SARS-Coronavirus (Mpro) with (PDB IDs: 2GTB and 3TNT) were downloaded from the Protein Data Bank (www.pdb.org), and any heteroatoms and water molecules were removed before molecular docking studies. Based on our molecular docking analysis we found that among all studied compounds, caulerpin has the highest binding affinity against all studied receptors 6LU7, 3TNT, and 2GTB with compared to some proposed antiviral drug currently used in COVID-19 treatment. abstract: This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski’s rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment. url: https://doi.org/10.1080/10934529.2020.1826192 doi: 10.1080/10934529.2020.1826192 id: cord-315193-z6v6s46n author: Adhikari, Nilanjan title: Structural Insight Into the Viral 3C-Like Protease Inhibitors: Comparative SAR/QSAR Approaches date: 2017-07-14 words: 9954.0 sentences: 585.0 pages: flesch: 59.0 cache: ./cache/cord-315193-z6v6s46n.txt txt: ./txt/cord-315193-z6v6s46n.txt summary: In the present report, quantitative structure-activity relationships (QSARs) techniques have been explored to understand the relation between the SARS-CoV 3CL pro and HRV 3C pro enzyme inhibitory activity with the physicochemical and structural properties of these inhibitors developed till now. (2008) reported some cinanserin analogs as SARS-CoV 3CL pro inhibitors (Table 11 .18), for which the QSAR model obtained was as shown by Eq. (2013b) reported a series of dipeptide-type SARS-CoV 3CL protease inhibitors (Table 11 .27) whose activity was shown to be controlled by the molar refractivity (CMR) and the polar volume (Pol Vol) of the compounds [Eq. QSAR models exhibited that the physicochemical parameters, such as dipole moment, PSA, polar volume, hydrophobicity, molar refractivity, SA, and molecular volume of the compounds play a crucial role in controlling both SARS-CoV 3CL pro and HRV 3C pro inhibitory activities. abstract: Severe acute respiratory syndrome (SARS), caused by SARS-coronavirus (SARS-CoV), is a dreadful infection worldwide having economic and medical importance and a global threat for health. It was turned into an epidemic in South China followed by a chain of infections across three generations. A number of pathogeneses in human may occur due to the virus. This infection has not been taken into account before the SARS outbreak, and still it is a neglected one. Therefore, there is an urgent need to develop small molecule antivirals to combat the SARS-CoV. No vaccines are available till date though a number of SARS-CoV 3C-like and 3C protease inhibitors were reported. In this chapter, quantitative structure–activity relationship technique is used for development of anti-SARS and anti-HRV drugs and outcome discussed in details. This approach may be a useful strategy to design novel and potential anti-SARS drugs to combat these dreadful viral diseases. url: https://api.elsevier.com/content/article/pii/B9780128097120000113 doi: 10.1016/b978-0-12-809712-0.00011-3 id: cord-309052-3h0g7s9v author: Alam, Fiaz title: Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review date: 2017-12-15 words: 9659.0 sentences: 569.0 pages: flesch: 46.0 cache: ./cache/cord-309052-3h0g7s9v.txt txt: ./txt/cord-309052-3h0g7s9v.txt summary: The Lymphangiogenesis inhibition (Jeong et al., 2013) Anti-Alzheimer (Chen et al., 2013) Carboxylesterase inhibitors 33 Isobavachin Flavonoid Seed/fruit Osteoblast (Li et al., 2014) 34 Isopsoralen Furanocoumarin Whole plant Antiprotozoal 35 Neobavaisoflavone Seeds Antibacterial (Khatune et al., 2004) 36 Psoralen Furanocoumarin Whole plant/root Leucoderma, psoriasis Anticancer (Hao et al., 2014) , antioxidant , anti-Alzheimer (Somani et al., 2015) , Collagengenesis 37 Psoralidin Coumarin Whole plant/seed Estrogen receptor modulator (Liu et al., 2014; Lim et al., 2011) Antioxidant (Wang, Yin, Zhang, Peng, & Kang, 2013b) , antibacterial (Khatune et al., 2004) Anti-diabetic (Behloul & Wu, 2013) , antiprotozoal Anticancer (Hao et al., 2014; Limper et al., 2013; Yang et al., 1996) , anti-depressent (Farahani et al., 2015) 38 Psoracorylifol D Flavonoid Seed Lymphangiogenesis inhibition (Jeong et al., 2013) Psoracoumestan Coumestans Seeds essential oil Anti-cancer (Limper et al., 2013) 39 Xanthoangelol Chalcone Seeds Anticancer (Limper et al., 2013) FIGURE 2 Structures of important compounds isolated from Psoralea corylifolia psoralester is a 10-membered lactone compound and the latter is an isomer of already known compound bayachromene (Tewari & Bhakuni, 2010) . abstract: Psoralea corylifolia L. (Leguminosae) is a well‐known traditional medicinal plant used from ancient times for treatment of various ailments. It is widely distributed and an important part of therapeutics in Ayurveda and in Chinese medicines. The aim of this review is to present comprehensive and most up to date report on its ethnobotanical, ethnopharmacological, clinical, phytochemical, and side effects. Studies on the ethnobotanical, ethnopharmacological, clinical, phytochemical, and side effects of P. corylifolia were published until year 2017 and were searched using various scientific databases. The scientific literature searched revealed that these plant species has been extensively investigated in vivo and in vitro for various biological and phytochemical studies. It has cardiotonic, vasodilator, pigmentor, antitumor, antibacterial, cytotoxic, and anti‐helminthic properties and locally used for alopecia, inflammation, leukoderma, leprosy, psoriasis, and eczema. So far, about a hundred bioactive compounds have been isolated from seeds and fruits, and most important compounds identified belongs to coumarins, flavonoids, and meroterpenes groups. This review article summarized the most updated scientific literature on bioactive phytochemical and biological activities of P. corylifolia. This article will be a useful addition to providing information for future research, and more standard clinical trials are needed for the plant to be used as therapeutic agent. url: https://doi.org/10.1002/ptr.6006 doi: 10.1002/ptr.6006 id: cord-352844-wggg3ynb author: Annunziata, Francesca title: An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities date: 2020-06-29 words: 50752.0 sentences: 2326.0 pages: flesch: 42.0 cache: ./cache/cord-352844-wggg3ynb.txt txt: ./txt/cord-352844-wggg3ynb.txt summary: Again, the coumarin derivative showed inhibitory activity on 15-LOX-1 in PC3 and DU145 cell lines, thus inducing apoptosis of the cancer cell, with the same mechanism of The results represent a good starting point for the design of novel derivatives, because most of the examined compounds exhibited selective toxicity on HeLa cells (IC 50 values between 136.4 ± 1.90 µM and 172.2 ± 1.80 µM after 24 h), whereas no negative effects on HDF normal cell''s growth was detected. Since tacrine is a well-known inhibitor of the catalytic site of AChE, whereas coumarins showed affinity for the peripheral anionic site (PAS) [161] , this new compounds may be potential dual-and therefore more powerful -inhibitors of ChEs. The in vitro AChE and BuChE inhibitory activity was evaluated using the Ellman''s method [159] ; among all the tested molecules, compound 105 resulted the best in AChE inhibition (IC 50 Thanks to their simple structural architecture and chemical stability, coumarins can be easily synthesized and modified in order to produce more active and selective compounds. abstract: Privileged structures have been widely used as an effective template for the research and discovery of high value chemicals. Coumarin is a simple scaffold widespread in Nature and it can be found in a considerable number of plants as well as in some fungi and bacteria. In the last years, these natural compounds have been gaining an increasing attention from the scientific community for their wide range of biological activities, mainly due to their ability to interact with diverse enzymes and receptors in living organisms. In addition, coumarin nucleus has proved to be easily synthetized and decorated, giving the possibility of designing new coumarin-based compounds and investigating their potential in the treatment of various diseases. The versatility of coumarin scaffold finds applications not only in medicinal chemistry but also in the agrochemical field as well as in the cosmetic and fragrances industry. This review is intended to be a critical overview on coumarins, comprehensive of natural sources, metabolites, biological evaluations and synthetic approaches. url: https://doi.org/10.3390/ijms21134618 doi: 10.3390/ijms21134618 id: cord-283301-adjjkqt2 author: Awolade, Paul title: Therapeutic significance of β-glucuronidase activity and its inhibitors: A review date: 2020-02-01 words: 18960.0 sentences: 1000.0 pages: flesch: 38.0 cache: ./cache/cord-283301-adjjkqt2.txt txt: ./txt/cord-283301-adjjkqt2.txt summary: Based on the foregoing, we extrapolate that the development of potent, specific and non-cytotoxic inhibitors of bGLU is imperative to improving the clinical efficacy of therapeutic agents and effective disease management while bearing in mind the physiological significance of both human and bacterial orthologs of the glycosyl hydrolase. Considering the proven and encouraging potentials of enzyme inhibition and molecular target therapy in drug development, and in continuation of our exploits and expositions thereon [54e58], herein we present a comprehensive review of research undertakings in the present millennium (2000e2019) directed towards the development of potent inhibitors of bGLU that are either natural products or synthetic scaffolds. In a study which examined the protective effects of thymol (54, Fig. 9 ) on inflammation in isoproterenol-induced myocardial infarction using male albino Wistar rats [167] , the therapeutic benefit of inhibiting the release of bGLU, other lysosomal enzymes and pro-inflammatory cytokines was evident in the restoration of near-normal myocardial histology and function, compared to diseased controls. abstract: The emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man’s existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, β-glucuronidase (βGLU) – a lysosomal acid hydrolase responsible for the catalytic deconjugation of β-d-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme’s activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of βGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of βGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved βGLU inhibitory potency and the development of new therapeutic agents in consequential. url: https://www.ncbi.nlm.nih.gov/pubmed/31835168/ doi: 10.1016/j.ejmech.2019.111921 id: cord-296560-ehrww6uu author: Bender, Andreas title: Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR date: 2006-11-07 words: 10156.0 sentences: 417.0 pages: flesch: 40.0 cache: ./cache/cord-296560-ehrww6uu.txt txt: ./txt/cord-296560-ehrww6uu.txt summary: This chapter discusses recent developments in some of the areas that exploit the molecular similarity principle, novel approaches to capture molecular properties by the use of novel descriptors, focuses on a crucial aspect of computational models—their validity, and discusses additional ways to examine data available, such as those from high-throughput screening (HTS) campaigns and to gain more knowledge from this data. The chapter also presents some of the recent applications of methods discussed focusing on the successes of virtual screening applications, database clustering and comparisons (such as drugand in-house-likeness), and the recent large-scale validations of docking and scoring programs. (Note that this has at the same time been shown empirically in virtual screening experiments [42, 43] .) Some of the methods, namely mutual information and genetic programing, have also been evaluated separately for their use in QSAR studies [44] with respect to a dataset which showed some (typical) problems present in the area, such as a very different sizes of ''active'' vs. abstract: This chapter discusses recent developments in some of the areas that exploit the molecular similarity principle, novel approaches to capture molecular properties by the use of novel descriptors, focuses on a crucial aspect of computational models—their validity, and discusses additional ways to examine data available, such as those from high-throughput screening (HTS) campaigns and to gain more knowledge from this data. The chapter also presents some of the recent applications of methods discussed focusing on the successes of virtual screening applications, database clustering and comparisons (such as drug- and in-house-likeness), and the recent large-scale validations of docking and scoring programs. While a great number of descriptors and modeling methods has been proposed until today, the recent trend toward proper model validation is very much appreciated. Although some of their limitations are surely because of underlying principles and limitations of fundamental concepts, others will certainly be eliminated in the future. url: https://www.ncbi.nlm.nih.gov/pubmed/32362803/ doi: 10.1016/s1574-1400(06)02009-3 id: cord-328962-1c4vqaqr author: Benítez-Cardoza, Claudia Guadalupe title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug date: 2020-06-15 words: 3344.0 sentences: 184.0 pages: flesch: 54.0 cache: ./cache/cord-328962-1c4vqaqr.txt txt: ./txt/cord-328962-1c4vqaqr.txt summary: KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. We use the amino acids reported in the crystallographic structure of the interaction between the S-protein-RBD of SARS-CoV-2 and ACE2 (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353 and Arg357 in ACE2) [10] [22] , therefore, using the crystallographic structure of ACE2 (PDB 1R42), we carried out a Docking directed to these mentioned residues using a library of compounds (EXPRESS-pick Collection from Chembridge Corp.) to select the best compounds, and that these can affect the interaction between ACE2 and SARS-CoV-2, making these results an important contribution to establishing the foundations that allow the development of a drug that optimizes the resolution of this pandemic. abstract: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of ΔG(binding), the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests. url: https://www.sciencedirect.com/science/article/pii/S0024320520307207?v=s5 doi: 10.1016/j.lfs.2020.117970 id: cord-023584-yaxawqhj author: Bucknall, R.A. title: The Continuing Search for Antiviral Drugs date: 2008-04-10 words: 8497.0 sentences: 339.0 pages: flesch: 48.0 cache: ./cache/cord-023584-yaxawqhj.txt txt: ./txt/cord-023584-yaxawqhj.txt summary: Of course, if wide-spectrum leads appear, the choice of test virus may be irrelevant, but the antiviral compounds (as distinct from interferon inducers) known at present are characterized by their relatively limited spectrum of activity, e.g., methisazone is active only against poxviruses (Bauer and Sadler, 1960) and possibly adenoviruses (Bauer and Apostolov, 1966) ; l-aminoadamantane is active only against influenza A1 and As and not against other myxo-or paramyxoviruses (Davies et al., 1964) ; guanidine and a-hydroxybenzyl benzimidazole are active only against picornaviruses and not against other small ribonucleic acid (RNA) viruses (Eggers and Tamm, 1961) . In summary, a tissue culture screen should be able to proccss large numbers of tcst compounds, using viruses as relevant as possible to the diseases for which a drug is required, and should employ normal rather than neoplastic cells. abstract: This chapter discusses the continuing search for antiviral drugs. Many virus diseases, both of humans and animals, have been successfully controlled by vaccines. These successes have naturally led to improvements in the spectrum and duration of protection offered by vaccines until, at present it is difficult to see how antiviral drugs could compete with vaccines in the control of many virus diseases. One may cite smallpox, yellow fever, polio, and recently measles among human diseases, Newcastle disease, Marek's disease, and infectious bronchitis among poultry diseases—an area of veterinary disease control where vaccines have been particularly important. Research into the treatment of virus diseases by drugs is at present directed toward three general areas: (1) attempts to stimulate the defense mechanism of the host animal, (2) large screening programs to find drugs which directly block some virus-specific process, and (3) alleviation of the symptoms of the disease. The treatment of the symptoms, rather than the cause of a disease, has been the mainstay of medical practice from time immemorial, and this is still the case with most virus disease. The short incubation period of many virus diseases will inevitably restrict the therapeutic use of antiviral drugs and in cases where symptoms have already appeared. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172480/ doi: 10.1016/s1054-3589(08)60460-3 id: cord-290539-8ak2tths author: Cagno, Valeria title: Novel broad spectrum virucidal molecules against enveloped viruses date: 2018-12-07 words: 5524.0 sentences: 276.0 pages: flesch: 51.0 cache: ./cache/cord-290539-8ak2tths.txt txt: ./txt/cord-290539-8ak2tths.txt summary: To further elucidate the mechanism of action we performed a virucidal assay in which 9d was incubated with the virus at 10 μM 5μM or 1μM concentration for different times (Fig 6A) or for 1h with serial dilutions of compound ( Fig 6B) ; subsequently, the mixture was titrated on cells and the viral titer was evaluated at dilutions at which the compound concentration was known not to be active in plaquing efficiency assays. The irreversibility of the mechanism was also tested with an assay in which the compound was incubated with the virus for 1h and subsequently the mixture has been diluted in drug free medium for additional 1, 2, 3 or 4 hours before the addition on cells (S2 Fig) . abstract: Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies. Here we report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes. Due to their selective action on enveloped viruses and to their lipid oxidation ability, we hypothesize a mechanism on the viral envelope that affects the fluidity of the lipid bilayer, thus compromising the efficiency of virus-cell fusion and preventing viral entry. url: https://doi.org/10.1371/journal.pone.0208333 doi: 10.1371/journal.pone.0208333 id: cord-103271-l9n27ocf author: Carozza, Jacqueline A title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 words: 5664.0 sentences: 329.0 pages: flesch: 51.0 cache: ./cache/cord-103271-l9n27ocf.txt txt: ./txt/cord-103271-l9n27ocf.txt summary: Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. Inspired by the molecular scaffold of a previous inhibitor, QS1, 26, 28 which lacks potency at physiological conditions, we build structure-activity relationships (SAR) around the three sections of the molecule -the zinc-binding head, the core, and the tail -and develop several inhibitors with nanomolar Ki values. Assays used to assess the potency of previously attempted ENPP1 inhibitors are inconsistent 26-34 ; however, developing an appropriate assay is key to determining the utility of the molecules in inhibiting cGAMP degradation under physiological conditions. Since our crystal structure suggests that the zinc-binding phosphonate head and quinazoline tail form the most important interactions with ENPP1, we next sought to explore the core region to achieve optimal geometry between these two functional groups ( Fig. 4a-b) . abstract: Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. An extracellular enzyme, ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), hydrolyzes cGAMP and negatively regulates this anti-cancer immune response. Small molecule ENPP1 inhibitors are much needed as tools to study basic biology of extracellular cGAMP and as investigational cancer immunotherapy drugs. Here, we surveyed structure-activity relationships around a series of cell-impermeable and thus extracellular-targeting phosphonate inhibitors of ENPP1. Additionally, we solved the crystal structure of an exemplary phosphonate inhibitor to elucidate the interactions that drive potency. This study yielded several best-in-class compounds with Ki < 2 nM and excellent physicochemical and pharmacokinetic properties. Finally, we demonstrate that an ENPP1 inhibitor delays tumor growth in a breast cancer mouse model. Together, we have developed ENPP1 inhibitors that are excellent tool compounds and potential therapeutics. url: https://doi.org/10.1101/2020.05.30.125534 doi: 10.1101/2020.05.30.125534 id: cord-034363-6uscua0y author: Cerda-Cavieres, Christopher title: Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands date: 2020-10-10 words: 7540.0 sentences: 384.0 pages: flesch: 52.0 cache: ./cache/cord-034363-6uscua0y.txt txt: ./txt/cord-034363-6uscua0y.txt summary: title: Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D(2) receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). Considering the pharmacological results, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds were carried out only in the human SERT (hSERT) and in selected cases at the D 2 receptor. Considering the pharmacological results, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds were carried out only in the human SERT (hSERT) and in selected cases at the D 2 receptor. abstract: A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D(2) receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D(2) ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D(2) receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D(2) receptor (D(2)/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure–activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q(2) = 0.625, 0.523 for CoMFA and CoMSIA and r(2)(ncv) = 0.967, 0.959 for CoMFA and CoMSIA, respectively). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594025/ doi: 10.3390/molecules25204614 id: cord-011251-rjyipcfv author: Chernyshov, Vladimir V. title: Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity date: 2019-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: ABSTRACT: An effective technique for one-stage synthesis of new polycyclic nitrogen-containing compounds has been developed. The procedure involves refluxing mixtures of camphoric acid with aliphatic or aromatic diamine without catalysts. In cases where the starting amine has a low boiling point (less than 200 °C), phenol is used as a solvent, as it is the most optimal one for obtaining products with good yields. It has been shown that the use of Lewis acids as catalysts reduces the yield of the reaction products. A set of compounds have been synthesized, which can be attributed to synthetic analogues of alkaloids. In vitro screening for activity influenza virus A was carried out for the obtained compounds. The synthesized quinazoline-like agent 14 has inhibitory activity against different strains of influenza viruses. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-019-09932-9) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223885/ doi: 10.1007/s11030-019-09932-9 id: cord-336759-cu1uprwm author: Cihan-Üstündağ, Gökçe title: Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives date: 2019-07-17 words: 2993.0 sentences: 183.0 pages: flesch: 55.0 cache: ./cache/cord-336759-cu1uprwm.txt txt: ./txt/cord-336759-cu1uprwm.txt summary: Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Based on these insights and our objective to optimize the antimicrobial activity of indolyl thiazolidinones and spirothiazolidinones, we here report the chemical synthesis, structural characterization and in vitro antitubercular, antiviral, antibacterial, and antifungal evaluation of new 5-chloro-3-phenyl-N(2,7,8,9substituted/nonsubstituted-3-oxo-1-thia-4-azaspiro [4.4] nonan/ [4.5] decan-4-yl)-1H-indole-2-carboxamides 4a-4i, 5a-5h (Fig. 1e ). As shown in Table 1 , compounds 4 h and 5h, bearing a phenyl substituent at position 8 of the spiro ring, exhibited the highest anti-TB activity at concentrations of 3.9 and 7.8 µM, respectively. The broad antibacterial and antifungal activity of compounds 4a-4i and 5a-5 h was further assessed using The experiment was performed twice and the same results were obtained a MIC, the actual minimum inhibitory concentration required to inhibit the growth of 100% of organisms abstract: ABSTRACT: A series of indole-based spirothiazolidinones have been designed, synthesized and evaluated, in vitro, for their antitubercular, antiviral, antibacterial, and antifungal activities. The structures of the new compounds were established by IR, (1)H NMR, (13)C NMR (proton decoupled, APT, and DEPT), electrospray ionization mass spectrometry, and microanalysis. Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Still, some of the tested compounds displayed activity on mycobacteria with MIC values of 16 and 31 µM. Four of the indole-spirothiazolidinone derivatives were found to be moderately active against Punta Toro virus, yellow fever virus or Sindbis virus in Vero cells. The antiviral EC(50) values were in the range of 1.9–12 µM and the selectivity index (ratio of cytotoxic to antivirally effective concentration) was above 10 in some cases. The most potent effect was seen with the compound that is methylated at positions 2 and 8 of the spirothiazolidinone system. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00706-019-02457-9) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/32214484/ doi: 10.1007/s00706-019-02457-9 id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 words: 9573.0 sentences: 487.0 pages: flesch: 43.0 cache: ./cache/cord-317628-1inxq7t5.txt txt: ./txt/cord-317628-1inxq7t5.txt summary: We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). abstract: Development of accurate disease models and discovery of immune-modulating drugs is challenged by the immune system’s highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable “phenomics” platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-β- and TNF-α-driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic. url: https://doi.org/10.1101/2020.08.02.233064 doi: 10.1101/2020.08.02.233064 id: cord-002237-200ondzx author: Dashtdar, Mehrab title: Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than Cloxacillin Against Pseudomonas Aeruginosa date: 2016-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVES: The purpose of this study was to obtain a natural antibiotic from Phenol-rich compounds; for the dressing and the treatment of chronic wounds. METHODS: The Phenol-rich compound sweet gel was prepared by blending four natural herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and Ephedra sinica stapf, with combination of a sweet gel medium, including honey, maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta indica gum as a stabilizer. The combinations were screened by using a well-diffusion assay with cloxacillin as a control. Pseudomonas spp. was tested with our novel antimicrobial compound. The zones of inhibition in agar culture were measured for each individual component and for the compound, and the results were compared with those of the control group which had been treated with cloxacillin. Data were expressed as means ± standard deviations. Quantitative analyses were performed using the paired t-test. RESULTS: The antibiotic effect of the Phenol-rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against Pseudomonas aeruginosa (P < 0.05). CONCLUSION: Our novel approach to fighting the antibiotic resistance of Pseudomonas proved to be successful. The Phenol-rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material, for the treatment of patients with various types of wounds, including burns, venous leg ulcers, ulcers of various etiologies, leg ulcers on the feet of diabetic, unhealed graft sampling sites, abscesses, boils, surgical wounds, necrotic process, post-operative and neonatal wound infection, and should be considered as an alternative to the usual methods of cure. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043089/ doi: 10.3831/kpi.2016.19.026 id: cord-253276-mqcwk2ow author: Desai, N. C. title: Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles date: 2013-09-30 words: 2623.0 sentences: 155.0 pages: flesch: 47.0 cache: ./cache/cord-253276-mqcwk2ow.txt txt: ./txt/cord-253276-mqcwk2ow.txt summary: The structure activity relationship revealed that the presence of electron withdrawing groups at para position of phenyl ring remarkably enhanced the antibacterial activity of synthesized compounds. From the results of the antimicrobial activity of the synthesized compounds 5ael, the following structure activity relationships can be derived: the antibacterial activity was considerably affected by substitution pattern on the phenyl ring and the most active compounds contain electron withdrawing substituent at para and meta positions of the phenyl ring (p > m > o). Compounds 5c and 5i, substituted with inductively electron withdrawing fluoro and nitro groups, respectively at para position showed the highest antibacterial activity (F > NO 2 ). While, substituting the phenyl ring with fluoro and nitro group at ortho position resulted in noticeable decrease in the antibacterial activity of compounds 5a and 5g respectively. The contrasting nature of substitution pattern at para position of the phenyl ring of most active antibacterial and antifungal agents indicate that the structural requirements are different for binding of drug to bacterial or fungal targets, respectively [43] . abstract: Abstract A series of thiazole clubbed 1,3,4-oxadiazole derivatives (5a–l) have been synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Synthesized compounds were evaluated for their antimicrobial and cytotoxic activities. The results indicated that, compounds 5c and 5i exhibited the most potent antibacterial activity. Compound 5f was found to be the most potent antifungal agent. The structure activity relationship revealed that the presence of electron withdrawing groups at para position of phenyl ring remarkably enhanced the antibacterial activity of synthesized compounds. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 5b, 5c, 5f, 5h and 5i is accompanied by low cytotoxicity. url: https://api.elsevier.com/content/article/pii/S0223523413003978 doi: 10.1016/j.ejmech.2013.06.029 id: cord-296970-5yc6u5t3 author: Donmez, Ataberk title: iBioProVis: interactive visualization and analysis of compound bioactivity space date: 2020-08-15 words: 2216.0 sentences: 131.0 pages: flesch: 52.0 cache: ./cache/cord-296970-5yc6u5t3.txt txt: ./txt/cord-296970-5yc6u5t3.txt summary: The sources of the set of compounds are not restricted; the compounds may be coming from a list of user-defined compounds indicated as canonical SMILES strings (e.g. the source of this list can be the output of a machine learning method, which predicts interacting compounds to the target of interest), drugs from DrugBank or target proteins'' active compounds that are extracted from a reliable compound-target bioactivity measurement dataset, which is a carefully processed and filtered subset of the ChEMBL (v25) database. We also provide a reliable compound-target bioactivity measurement dataset, which is a carefully processed and filtered subset of ChEMBL (v25) database, to be used with iBioProVis. iBioProVis is an interactive web-based visualization tool and it has advantages when compared with existing studies and tools. abstract: SUMMARY: iBioProVis is an interactive tool for visual analysis of the compound bioactivity space in the context of target proteins, drugs and drug candidate compounds. iBioProVis tool takes target protein identifiers and, optionally, compound SMILES as input, and uses the state-of-the-art non-linear dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) to plot the distribution of compounds embedded in a 2D map, based on the similarity of structural properties of compounds and in the context of compounds’ cognate targets. Similar compounds, which are embedded to proximate points on the 2D map, may bind the same or similar target proteins. Thus, iBioProVis can be used to easily observe the structural distribution of one or two target proteins’ known ligands on the 2D compound space, and to infer new binders to the same protein, or to infer new potential target(s) for a compound of interest, based on this distribution. Principal component analysis (PCA) projection of the input compounds is also provided, Hence the user can interactively observe the same compound or a group of selected compounds which is projected by both PCA and embedded by t-SNE. iBioProVis also provides detailed information about drugs and drug candidate compounds through cross-references to widely used and well-known databases, in the form of linked table views. Two use-case studies were demonstrated, one being on angiotensin-converting enzyme 2 (ACE2) protein which is Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein receptor. ACE2 binding compounds and seven antiviral drugs were closely embedded in which two of them have been under clinical trial for Coronavirus disease 19 (COVID-19). AVAILABILITY AND IMPLEMENTATION: iBioProVis and its carefully filtered dataset are available at https://ibpv.kansil.org/ for public use. CONTACT: vatalay@metu.edu.tr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. url: https://www.ncbi.nlm.nih.gov/pubmed/32407491/ doi: 10.1093/bioinformatics/btaa496 id: cord-300574-nclkfw4h author: Donno, Dario title: Chapter 9 Nutraceuticals in Alternative and Underutilized Fruits as Functional Food Ingredients: Ancient Species for New Health Needs date: 2018-12-31 words: 7915.0 sentences: 369.0 pages: flesch: 38.0 cache: ./cache/cord-300574-nclkfw4h.txt txt: ./txt/cord-300574-nclkfw4h.txt summary: Wild plant species are of interest to the food industry because of their ability to replace synthetic chemicals and nutraceuticals; however, the nutritional, economical, and sociocultural values of some neglected and underutilized natural resources have not yet been fully exploited. Some of these less well-known and underutilized fruits, which have the potential to provide novel sources of health-promoting agents, are presented in this chapter (i.e., Asimina triloba (L.) Dunal, Crataegus azarolus L., Lycium barbarum L., Morus nigra L., and Amelanchier canadensis (L.) Medicus). A diet containing high levels of fruits and vegetables has been associated with a lower risk of chronic diseases because, in addition to their high vitamin and mineral content, these foods also contain compounds with health-protective effects, in particular antioxidant and antiinflammatory compounds (Donno et al., 2013b) . Mulberries are sweet fruits and they play an important role in the food industry due to their high levels of bioactive compounds (mulberry fruits can vary in terms of their chemical composition and antioxidant properties). abstract: Abstract A diet containing high levels of fruit has been associated with a lowered risk of chronic diseases as, in addition to their vitamin and mineral content, they also contain various compounds with health-protective effects, in particular antioxidant and antiinflammatory compounds. Wild plant species are of interest to the food industry because of their ability to replace synthetic chemicals and nutraceuticals; however, the nutritional, economical, and sociocultural values of some neglected and underutilized natural resources have not yet been fully exploited. Some of these less well-known and underutilized fruits, which have the potential to provide novel sources of health-promoting agents, are presented in this chapter (i.e., Asimina triloba (L.) Dunal, Crataegus azarolus L., Lycium barbarum L., Morus nigra L., and Amelanchier canadensis (L.) Medicus). Underutilized fruits could represent an opportunity for growers to gain access to these special markets where consumers place emphasis on high contents of nutrients that are capable of preventing degenerative diseases. The development of specific horticultural models for nutraceutical fruit production could be an interesting opportunity to obtain a highly standardized raw material for fresh or derived products. url: https://www.sciencedirect.com/science/article/pii/B9780128114469000095 doi: 10.1016/b978-0-12-811446-9.00009-5 id: cord-347547-makm0j09 author: Duran-Frigola, Miquel title: Bioactivity Profile Similarities to Expand the Repertoire of COVID-19 Drugs date: 2020-07-16 words: 1942.0 sentences: 99.0 pages: flesch: 46.0 cache: ./cache/cord-347547-makm0j09.txt txt: ./txt/cord-347547-makm0j09.txt summary: By comparing the set of drugs reported to be potentially active against SARS-CoV-2 to a universe of 1 million bioactive molecules, we identify compounds that display analogous chemical and functional features to the current COVID-19 candidates. Searches can be filtered by level of evidence and mechanism of action, and results can be restricted to drug molecules or include the much broader space of bioactive compounds. Indeed, we conducted a limited review of the most relevant scientific literature and identified over 200 compounds that are potentially active against COVID-19 with different levels of experimental support, from purely computational predictions to preclinical and drugs already in clinical trials. We use the list of COVID-19 compounds extracted from the literature, with different levels of experimental evidence, as bait to search for compounds with similar bioactivity or chemical features among the 800,000 molecules contained in the CC. abstract: [Image: see text] Until a vaccine becomes available, the current repertoire of drugs is our only therapeutic asset to fight the SARS-CoV-2 outbreak. Indeed, emergency clinical trials have been launched to assess the effectiveness of many marketed drugs, tackling the decrease of viral load through several mechanisms. Here, we present an online resource, based on small-molecule bioactivity signatures and natural language processing, to expand the portfolio of compounds with potential to treat COVID-19. By comparing the set of drugs reported to be potentially active against SARS-CoV-2 to a universe of 1 million bioactive molecules, we identify compounds that display analogous chemical and functional features to the current COVID-19 candidates. Searches can be filtered by level of evidence and mechanism of action, and results can be restricted to drug molecules or include the much broader space of bioactive compounds. Moreover, we allow users to contribute COVID-19 drug candidates, which are automatically incorporated to the pipeline once per day. The computational platform, as well as the source code, is available at https://sbnb.irbbarcelona.org/covid19. url: https://www.ncbi.nlm.nih.gov/pubmed/32672454/ doi: 10.1021/acs.jcim.0c00420 id: cord-006139-9063uhox author: Egan, Timothy J title: Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter date: 2013-03-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Malaria remains a major international health challenge. Resistance to a number of existing drugs and evidence of the emergence of artemisinin resistance has emphasized the need for new antimalarials. A new approach has been the preparation of dual-function compounds that include a chloroquine-like antimalarial group and a group that resembles a chloroquine chemosensitizer. This article reviews the recent discovery of such dual-function antimalarials that are proposed to target both hemozoin formation and the chloroquine resistance transporter, PfCRT. These are discussed in relation to the mechanism of action of 4-aminoquinolines, chloroquine resistance and resistance reversal. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099626/ doi: 10.2217/fmb.13.18 id: cord-003427-0dddrh4e author: El-Faham, Ayman title: Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives date: 2015-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC(50) values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC(50) 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC(50) value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332339/ doi: 10.3390/molecules200814638 id: cord-270123-m8utyd1m author: Enmozhi, Sukanth Kumar title: Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach date: 2020-05-05 words: 3873.0 sentences: 187.0 pages: flesch: 49.0 cache: ./cache/cord-270123-m8utyd1m.txt txt: ./txt/cord-270123-m8utyd1m.txt summary: This paper evaluates the compound Andrographolide from Andrographis paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction and ADME prediction. And upon certain in vitro and some clinical data chloroquine phosphate and hydroxychloroquine sulphate was advised to be the treatment for COVID-19 and enough randomized trials on these compounds to be provided and allowed the administration of the above drugs to be used for emergency (https://www.fda.gov/emergency-use-authori-zation#covidtherapeutics). Though there are many targets are found for the treatment of COVID-19, the main protease (M pro ) of SARS-CoV-2 was chosen due to interest of treating infected patients, to stop the multiplication of virus within the cells, through which M pro was involved in the release of polypeptides which are functional extensive proteolysis and cleavage of the enzyme itself from the sites of genome, pp1a and ppa1ab . abstract: SARS-CoV-2 virus which caused the global pandemic the Coronavirus Disease- 2019 (COVID-2019) has infected about 1,203,959 patients and brought forth death rate about 64,788 among 206 countries as mentioned by WHO in the month of April 2020. The clinical trials are underway for Remdesivir, an investigational anti-viral drug from Gilead Sciences. Antimalarial drugs such as Chloroquine and Hydroxychloroquine derivatives are being used in emergency cases; however, they are not suitable for patients with conditions like diabetes, hypertension and cardiac issues. The lack of availability of approved treatment for this disease calls forth the scientific community to find novel compounds with the ability to treat it. This paper evaluates the compound Andrographolide from Andrographis paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction and ADME prediction. Andrographolide was docked successfully in the binding site of SARS-CoV-2 Mpro. Computational approaches also predicts this molecule to have good solubility, pharmacodynamics property and target accuracy. This molecule also obeys Lipinski’s rule, which makes it a promising compound to pursue further biochemical and cell based assays to explore its potential for use against COVID-19. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1760136 doi: 10.1080/07391102.2020.1760136 id: cord-261170-arnwk287 author: Gallimore, W. title: Chapter 18 Marine Metabolites Oceans of Opportunity date: 2017-12-31 words: 7118.0 sentences: 404.0 pages: flesch: 41.0 cache: ./cache/cord-261170-arnwk287.txt txt: ./txt/cord-261170-arnwk287.txt summary: Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. To gain an understanding of the importance of marine natural products chemistry in drug development G To be able to map the process involved in drug development from marine natural products G To gain an appreciation of the range of biological activities associated with compounds isolated from micro-and macroorganisms G To identify the marine-derived drugs which are undergoing clinical evaluation Biological activities identified in extracts and metabolites of algal origin include anticancer, antiobesity, neuroprotective, and antioxidant activity and Scheme 18.2 shows chemical structures of representative bioactive compounds isolated from the macroalgae. Biologically active compounds from marine bacteria also include Streptomyces species from sediment and fish gut from which anticancer (e.g., halichomycin and δ-indomycinone) and antibacterial agents (e.g., phenazines) have been obtained [58À60]. abstract: Abstract The marine environment provides an array of compounds often with unique molecular architectures boasting an equally wide array of bioactivities including anticancer, antiinflammatory, and antimicrobial activity. Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. The pharmaceutical industry has benefited from research into marine metabolites with the development of marine-derived drugs including cytarabine, vidarabine, and ziconotide along with the more recently developed formulation Carragelose, an antiviral spray. Cosmetic applications incorporating marine extracts include Abyssine and RefirMAR. Research with macroinvertebrates, macroalgae, and microorganisms continue in the hope that drugs of the future will be culled from the oceans of the world. While obtaining a consistent and adequate supply of the bioactive compounds remains a challenge to be overcome, synthetic methods are being employed along with the application of biotechnological techniques to ensure that the drugs, when developed, will be in sufficient quantities for distribution to those who are in need. url: https://api.elsevier.com/content/article/pii/B9780128021040000184 doi: 10.1016/b978-0-12-802104-0.00018-4 id: cord-293867-c4wnr5xe author: Gürsoy, Elif title: Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents date: 2019-12-06 words: 2974.0 sentences: 156.0 pages: flesch: 50.0 cache: ./cache/cord-293867-c4wnr5xe.txt txt: ./txt/cord-293867-c4wnr5xe.txt summary: Besides the wide biological activity spectrum of imidazo[2,1-b] thiazole derivatives, also the compounds bearing hydrazide, acyl-hydrazone and spirothiazolidinone moiety, have been reported in the literature with their various effects such as antibacterial [21] , antifungal [22] , antitubercular [23] , antiviral [24] , anticonvulsant [25] and antidepressant [26] . In this study, we further explored the scaffold containing the imidazo [2,1-b] thiazole ring as the aromatic moiety, that is linked by an amide to a spirothiazolidinone ring system as the aliphatic cyclic moiety and from this point forward, novel derivatives were synthesized (Table 1) , and broadly evaluated for their antiviral and antimycobacterial activity (Fig. 2) . General procedure for the synthesis of 6-(4-bromophenyl)-N 2 -(substituted/non-substituted cycloalkylidene)imidazo[2,1-b]thiazole-3-acetohydrazides (4a-d) 0,005 mol of 3 was boiled in a water bath under reflux with 30 mL of ethanol until a clear solution was obtained. abstract: A series of novel acyl-hydrazone (4a-d) and spirothiazolidinone (5a-d, 6a-d) derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antiviral and antimycobacterial activity. The antituberculosis activity was evaluated by using the Microplate Alamar Blue Assay and the antiviral activity was evaluated against diverse viruses in mammalian cell cultures. According to the biological activity studies of the compounds, 5a-c displayed hope promising antitubercular activity, 6d was found as potent for Coxsackie B4 virus, 5d was found as effective against Feline corona and Feline herpes viruses. Consequently, the obtained results displayed that, 5a-d and 6d present a leading structure for future drug development due to its straightforward synthesis and relevant bioactivity. url: https://www.sciencedirect.com/science/article/pii/S0045206819309988 doi: 10.1016/j.bioorg.2019.103496 id: cord-333675-vkk2frnf author: Hamada, Manabu title: Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides date: 2013-07-04 words: 4256.0 sentences: 234.0 pages: flesch: 56.0 cache: ./cache/cord-333675-vkk2frnf.txt txt: ./txt/cord-333675-vkk2frnf.txt summary: A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. N 1crotyl-1,2,4-triazole-3-bis-Boc-carboxamide 19 was then subjected to the olefin cross metathesis reaction, with bis(POM)-allylphosphonate in CH 2 Cl 2 to obtain the desired compound 20 in 16% yield. The title bis(POM) (E)-4-phosphono-but-2-en-1-yl acyclic nucleosides were subjected to an in vitro antiviral screening using a wide spectrum of viruses, in MDKC cell cultures for anti-influenza virus activity, in Vero cell cultures for an antiviral activity against Para-influenza3 shown) only compound 31 showed activity at an EC 50 of w10 mM (AD-169 strain) with no observed cytotoxicity at 100 mM ( Table 2) . abstract: A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC(50) of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM. url: https://api.elsevier.com/content/article/pii/S0223523413004212 doi: 10.1016/j.ejmech.2013.06.053 id: cord-252108-04xr5xdl author: Havrylyuk, Dmytro title: Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones date: 2013-06-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A series of novel 5-pyrazoline substituted 4-thiazolidinones have been synthesized. Target compounds were evaluated for their anticancer activity in vitro within DTP NCI protocol. Among the tested compounds, the derivatives 4d and 4f were found to be the most active, which demonstrated certain sensitivity profile toward the leukemia subpanel cell lines with GI(50) value ranges of 2.12–4.58 μM (4d) and 1.64–3.20 μM (4f). The screening of antitrypanosomal and antiviral activities of 5-(3-naphthalen-2-yl-5-aryl-4,5-dihydropyrazol-1-yl)-thiazolidine-2,4-diones was carried out with the promising influence of the mentioned compounds on Trypanosoma brucei, but minimal effect on SARS coronavirus and influenza types A and B viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/23811085/ doi: 10.1016/j.ejmech.2013.05.044 id: cord-033493-kslzdy8q author: Hebishy, Ali M. S. title: New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity date: 2020-09-21 words: 3385.0 sentences: 186.0 pages: flesch: 50.0 cache: ./cache/cord-033493-kslzdy8q.txt txt: ./txt/cord-033493-kslzdy8q.txt summary: title: New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity [Image: see text] This study describes a new route to the synthesis of novel benzamide-based 5-aminopyrazoles and their corresponding pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives. 5-Aminopyrazole 4 was prepared by alkylation of the potassium 2-cyano-ethylene-1thiolate salt 2 with an alkyl halide at room temperature to offer N-(2,2-dicyano-1-(alkylthio)vinyl)benzamide 3 followed by a reaction with hydrazine hydrate by refluxing ethanol containing a catalytic amount of piperidine (Scheme 1). The antiviral activity was measured for the synthesized compounds with respect to the H5N1 influenza virus strain A/Egypt/M7217B/2013 using MTT 50 ) and plaque reduction assays 52 exploring the cytotoxicity and inhibition percentage values, respectively. Design, synthesis, docking, and antimicrobial evaluation of some novel pyrazolo[1,5-a] pyrimidines and their corresponding cycloalkane ring-fused derivatives as purine analogs abstract: [Image: see text] This study describes a new route to the synthesis of novel benzamide-based 5-aminopyrazoles and their corresponding pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives. Benzamide-based 5-aminopyrazoles were prepared through a reaction of benzoyl isothiocyanate with malononitrile in KOH–EtOH followed by alkylation with alkyl halides and then a reaction with hydrazine. In an attempt to react benzoyl isothiocyanate with ethyl cyanoacetate in KOH–EtOH followed by alkylation with methyl iodide at room temperature and then a reaction with hydrazine has resulted in the formation of 3-ethoxy-5-phenyl-1H-1,2,4-triazole. The structures of the new compounds were characterized by mass spectroscopy, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy, infrared spectroscopy (IR), and X-ray analysis. The new compounds were tested in vitro for their anti-influenza A virus (subtype H5N1) activity. Among the synthesized compounds, eight compounds 3b, 4, 10b, 10c, 12a, 19, 21a, and 21b were found to possess significant antiviral activities against bird flu influenza (H5N1) with viral reduction in the range of 85–65%. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542596/ doi: 10.1021/acsomega.0c02675 id: cord-000536-0mn1gbll author: Hu, Le-Le title: Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions date: 2011-12-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248422/ doi: 10.1371/journal.pone.0029491 id: cord-292380-ulsejzqt author: Iwanejko, Jakub title: Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells date: 2020-05-22 words: 6156.0 sentences: 349.0 pages: flesch: 52.0 cache: ./cache/cord-292380-ulsejzqt.txt txt: ./txt/cord-292380-ulsejzqt.txt summary: Bearing in mind the remarkable precedents of improving the efficacy of cytotoxicity against cancer cell lines by insertion of aminophosphonate moiety and the results of our previous research, we directed our examinations toward the evaluation of antiproliferative properties of the phosphonic derivatives of octahydroquinoxalin-2(1H)-one. Bearing in mind the remarkable precedents of improving the efficacy of cytotoxicity against cancer cell lines by insertion of aminophosphonate moiety and the results of our previous research, we directed our examinations toward the evaluation of antiproliferative properties of the phosphonic derivatives of octahydroquinoxalin-2(1H)-one. Afterwards, wells were washed five times with water and 50 µL of 0.4% solution of SRB (sulforhodamine B, Sigma-Aldrich Chemie GmbH, Steinheim, Germany) in 1% acetic acid (POCh, Gliwice, Poland) was added to each well and plates were again incubated at RT for 30 min. The unbound dye was removed by washing plates five times with 1% acetic acid, while stained cells were treated with 10 mM TRIS (Tris base, Sigma-Aldrich, Chemie GmbH, Steinheim, Germany). abstract: In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction. url: https://www.ncbi.nlm.nih.gov/pubmed/32455965/ doi: 10.3390/ma13102393 id: cord-014863-jyti99xq author: Karaküçük-İyidoğan, A. title: Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents date: 2019-05-15 words: 3517.0 sentences: 516.0 pages: flesch: 69.0 cache: ./cache/cord-014863-jyti99xq.txt txt: ./txt/cord-014863-jyti99xq.txt summary: Encouraged by these results and aimed at developing effective anticancer agents, we designed two series of thiosemicarbazones by the pharmacophore hybridization method using two or more different pharmacophores in view of prospecting their cytostatic and antiviral activity (Fig. 1) . The synthesized compounds were also evaluated for their cytostatic activity against murine leukemia L1210, human CD 4 + T-lymphocyte CEM and cervix carcinoma HeLa cells (Table 4 ). The results showed that compounds Ia -Ig containing electron-withdrawing group, such as -CN located at the para position of the benzene ring, increased the cytostatic activity, according to the electron-donating group (-SCH 3 ) at the same position of the structure (like compounds Synthesis, Biological Evaluation and Ligand 147 IIa -IIg). It is established that Hb-acceptor (-CN; -SCH 3 ), hydrophobic groups (-N(CH 2 CH 2 Cl) 2 ), and 3D-conformations are responsible for the cytostatic activity of compounds such as Ig and IIg, according to ligand-based pharmacophore modeling. abstract: Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC(50) = 13 – 27 μg/mL for strain H1N1 and 9.3 – 18 μg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC(50) = 0.3 μg/mL for Ig and 1.9 μg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC(50) of 0.30, 0.70 and 2.50 μg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089137/ doi: 10.1007/s11094-019-01968-3 id: cord-344598-5drr3fyt author: Khanna, Leena title: Spiro‐Indole‐Coumarin Hybrids: Synthesis, ADME, DFT, NBO Studies and In Silico Screening through Molecular Docking on DNA G‐Quadruplex date: 2020-03-19 words: 3901.0 sentences: 264.0 pages: flesch: 56.0 cache: ./cache/cord-344598-5drr3fyt.txt txt: ./txt/cord-344598-5drr3fyt.txt summary: Thus, in the present study, the biological importance of 22 compounds including six new spiro indole-coumarin hybrids as DNA quadruplex groove binders has been evaluated by performing molecular docking studies on DNA G-quadruplexes of the human genome. Finally, Density Functional Theory (DFT) calculations, NBO analysis, and MEP plots are drawn for hybrids to prove their chemical reactivity and stability. 1 H NMR spectrum showed the presence of methylene of thiazolidine as two doublets at δ 4.37 and δ 4.05 besides the usual aromatic protons of indole, indazole and coumarin moieties. Table 1 also shows all six newly synthesized spiro indolecoumarin hybrids 10 a-c and 12 a-c are having high binding energy as compared to intermediary Schiff bases, isatin, their non-hybrid counterparts and the reference compounds. Binding interaction of about 22 compounds including these hybrids with DNA G-quadruplex of the human genome, was screened using Molecular docking studies. abstract: New series of hybrids were synthesized by combination of 4‐hydroxycoumarin with spiro[indol‐indazole‐thiazolidine]‐diones and spiro[indol‐pyrazole‐thiazolidine]‐diones, via hitherto unknown Schiff bases. The effects of substituents, such as ‐F, ‐Br and ‐CH(3), on the crucial characteristics pertaining to the hybrids were investigated through computational studies. In silico or virtual screening through molecular docking studies on the library of 22 compounds, including reference compounds, precursors, non‐hybrid and hybrid derivatives, was performed on DNA G‐quadruplex of the human genome. All six freshly synthesized hybrids showed high binding energy as compared to non‐hybrids as well as reference compounds. The presence of substituents at 5‐position of indole enhanced the binding tendency of the ligand. ADME studies indicated good oral bioavailability and absorption of these compounds. Density Functional Theory (DFT) calculations of hybrids were done at B3LYP/6‐311G++(d,p) level of computation. Their HOMO and LUMO energy plots reflected the presence of high charge transfer and chemical potential. Natural bond order (NBO) calculations predicted hyperconjugative interactions. The Molecular Electrostatic Potential (MEP) surface plots showed possible electrophilic and nucleophilic attacking sites of the hybrids. Compound 10 a (5‐fluoro‐spiro[indol‐indazole‐thiazolidine]‐dione‐coumarin hybrid), on the basis of global reactivity descriptors, was filtered to be chemically most reactive with the highest binding energy of −8.23 kcal/mol with DNA G‐quadruplex. The synthesized hybrid coumarin derivatives in correlation with theoretical docking studies validate that hybrid derivatives are more reactive compared to their non‐hybrid counterparts. url: https://www.ncbi.nlm.nih.gov/pubmed/32328514/ doi: 10.1002/slct.201904783 id: cord-255862-84u3c33m author: Kim, Ji Won title: Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut) date: 2017-07-01 words: 2843.0 sentences: 172.0 pages: flesch: 61.0 cache: ./cache/cord-255862-84u3c33m.txt txt: ./txt/cord-255862-84u3c33m.txt summary: In this research, we investigated whether escin derivatives 1–7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Interestingly, compounds 1-7 isolated from the fraction with the two-step hydrolysis were evaluated to have much lower cytotoxic effects than compounds 8-10 from the n-BuOH part at concentration of 20 lM (Fig. S22) . As compounds 8-10 showed strong cytotoxic effects on Vero cells at 20 lM, their PEDV inhibitory activities were evaluated at a concentration of 2 lM. 33 To measure the expression level of viral RNA encoding nucleocapsid and spike proteins, compounds 4 and 6 were treated in Vero cells at a concentration of 40 lM and total RNA was extracted for reverse transcription followed by polymerase chain reaction using the primers for PEDV (STable 1 ). abstract: Abstract Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high fatality of piglets, influencing the swine industry. Japanese horse chestnut (seed of Aesculus turbinata) contains many saponin mixtures, called escins, and has been used for a long time as a traditional medicinal plant. Structure-activity relationship (SAR) studies on escins have revealed that acylations at C-21 and C-22 with angeloyl or tigloyl groups were important for their cytotoxic effects. However, the strong cytotoxicity of escins makes them hard to utilize for other diseases and to develop as nutraceuticals. In this research, we investigated whether escin derivatives 1–7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Compounds 1–7 had no cytotoxicity at 20μM on VERO cells, while compounds 8–10 showed strong cytotoxicity at similar concentrations on PEDV. Our results suggest that escin derivatives showed strong inhibitory activities on PEDV replication with lowered cytotoxicity. These studies propose a method to utilize Japanese horse chestnut for treating PEDV and to increase the diversity of its bioactive compounds. url: https://doi.org/10.1016/j.bmcl.2017.05.022 doi: 10.1016/j.bmcl.2017.05.022 id: cord-345750-dk1exw9l author: Kulikov, A. S. title: Synthesis and antineoplastic properties of (1H-1,2,3-triazol-1-yl)furazans date: 2014-01-07 words: 2274.0 sentences: 188.0 pages: flesch: 67.0 cache: ./cache/cord-345750-dk1exw9l.txt txt: ./txt/cord-345750-dk1exw9l.txt summary: All target compounds were evaluated for both antimitotic microtubule destabilizing effect in a phenotypic sea urchin embryo assay and cytotoxicity in a panel of 60 human cancer cell lines. Water soluble biologically active compounds contain ing both cycles, e.g., (1,2,3 triazol 1 yl)furazans 1, ex hibiting other mechanisms of action were synthesized. In addition, to extend the scope of triazolylfurazan derivatives with potential antineoplastic activity, we used the Clauson-Kaas pyrrole synthesis involving the reaction of primary amino group of the furazan ring with dimethoxytetra hydrofuran. Therefore, unpurified esters 4a-g were hydrolyzed to the corresponding acids 5a-g, which also without further purification were subsequently thermally decarboxylated to target 3 amino 4 [5 aryl(hetaryl) 1H 1,2,3 triazol 1 yl]furazans 6a-g in high yields. Subsequent Clauson-Kaas condensation of synthesized triazolylfurazans 6 with dimethoxytetrahydrofuran yielded a series of 4 [5 aryl (hetaryl) 1H 1,2,3 triazol 1 yl] (3 pyrrol 1 yl)furazans 7. abstract: A method of 3-amino-4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]furazan synthesis was optimized. Condensation of these compounds with 2,5-dimethoxytetrahydrofuran resulted in a series of previously unknown 4-[5-aryl(heteroaryl)-1H-1,2,3-triazol-1-yl)]-3-(pyrrol-1-yl)furazans. All target compounds were evaluated for both antimitotic microtubule destabilizing effect in a phenotypic sea urchin embryo assay and cytotoxicity in a panel of 60 human cancer cell lines. Pyrrolyl derivatives of triazolylfurazans were determined as antiproliferative compounds. The most potent microtubule targeting compounds 7a and 7e are of interest for further trials as antineoplastic agents. url: https://doi.org/10.1007/s11172-013-0113-2 doi: 10.1007/s11172-013-0113-2 id: cord-320591-re99v1qt author: Le, Thanh Ninh title: Bioactive Compounds and Bioactivities of Brassica oleracea L. var. Italica Sprouts and Microgreens: An Updated Overview from a Nutraceutical Perspective date: 2020-07-27 words: 8182.0 sentences: 395.0 pages: flesch: 34.0 cache: ./cache/cord-320591-re99v1qt.txt txt: ./txt/cord-320591-re99v1qt.txt summary: Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). In summary, previous studies showed that broccoli sprout extracts rich in vitamins, carotenoids, and phenolic compounds showed very high antioxidant activity in both in vitro and in vivo tests (Table 4) . Moreover, the previous studies have focused on several biological activities of broccoli seedlings, such as antioxidant, anticancer, antimicrobial, and anti-inflammatory, as well as the potentially beneficial effects for patients with cancers, diabetes, and obesity. abstract: Sprouts and microgreens, the edible seedlings of vegetables and herbs, have received increasing attention in recent years and are considered as functional foods or superfoods owing to their valuable health-promoting properties. In particular, the seedlings of broccoli (Brassica oleracea L. var. Italica) have been highly prized for their substantial amount of bioactive constituents, including glucosinolates, phenolic compounds, vitamins, and essential minerals. These secondary metabolites are positively associated with potential health benefits. Numerous in vitro and in vivo studies demonstrated that broccoli seedlings possess various biological properties, including antioxidant, anticancer, anticancer, antimicrobial, anti-inflammatory, anti-obesity and antidiabetic activities. The present review summarizes the updated knowledge about bioactive compounds and bioactivities of these broccoli products and discusses the relevant mechanisms of action. This review will serve as a potential reference for food selections of consumers and applications in functional food and nutraceutical industries. url: https://www.ncbi.nlm.nih.gov/pubmed/32727144/ doi: 10.3390/plants9080946 id: cord-013387-q91052qw author: Leão, Rozires P. title: Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach date: 2020-08-26 words: 12136.0 sentences: 651.0 pages: flesch: 43.0 cache: ./cache/cord-013387-q91052qw.txt txt: ./txt/cord-013387-q91052qw.txt summary: In this initial stage, the pivot molecule rofecoxib was used as a research model for the virtual screening in six commercial molecule databases: Chembridge DIVERSetEXP, DIVERSet CORE Library (https://www.chembridge.com) [24] , Maybridge Collections (www.maybridge.com) [25, 26] , ZINC Drug Database, ZINC Natural Stock (http://zinc.docking.org) [27] , and Drug FDA BindingDB (http://www.bindingdb.org) [27] using the programs Rapid Overlay of Chemical Structures (ROCS) and electrostatic similarity (EON). The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity. The bioactivity scores of the LMQC72, LMQC36, and LMQC50 structures were calculated for different parameters, as receptor binding of the ligand to the G protein coupled (GPCR) and nuclear receptor ligand, modulating ion channel, kinase inhibition, protease inhibition, and inhibition of enzyme activity. abstract: The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559105/ doi: 10.3390/ph13090209 id: cord-340832-412qre64 author: Liang, Pi‐Hui title: Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis date: 2006-01-05 words: 3832.0 sentences: 221.0 pages: flesch: 55.0 cache: ./cache/cord-340832-412qre64.txt txt: ./txt/cord-340832-412qre64.txt summary: In the screening for 166 www.chembiochem.org a-glucosidase (bakers'' yeast) inhibition, about two-thirds of reaction products were found to be more potent than 4 (see Supporting Information for overall library inhibitory activities). With the potent a-glucosidase inhibitors in hand, we tested their potential antiviral effect based on our previous assay system for JEV and DEN-2. [16] The weaker a-glucosidase inhibitors 39-41, derived from core 4 with eight to ten carbons (Scheme 3), were then evaluated, and we found that 39-41 at 10 or 50 mM did not inhibit either JEV or DEN-2 infection (data not shown) in the cell-based assay. The N-alkylated derivatives of compound 24 were also tested for antiviral activity, and 36-38, which contain lipophilic alkyl groups, were the most active, with an IC 50 of about 5-10 mM against JEV, DEN-2, and SARS-CoV infection. However, extending the alkyl chain at the ring nitrogen gave the most potent human b-hexosaminidase inhibitor known to date, that is, compound 54, with a K i value of 2.6 nM. abstract: A novel 5‐membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein‐processing α‐glucosidase with a K(i) value of 53 nm. This compound was further derivatized to antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN‐2), human SARS coronavirus, and human β‐hexosaminidase (K(i) =2.6 nm), a new target for the development of osteoarthritis therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/16397876/ doi: 10.1002/cbic.200500321 id: cord-273372-69rlh9or author: Litterman, Nadia title: Small molecules with antiviral activity against the Ebola virus date: 2015-02-09 words: 3257.0 sentences: 157.0 pages: flesch: 48.0 cache: ./cache/cord-273372-69rlh9or.txt txt: ./txt/cord-273372-69rlh9or.txt summary: In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. We have found that indeed there is much prior knowledge regarding small molecules that have been shown to be active against the Ebola virus in vitro or in animal models 10-13 , including a number of FDA-approved drugs 14-16 . Medicinal chemistry analysis of small molecules active against the Ebola virus We have recently described an expert''s medicinal chemistry 26 analysis of the over 320 NIH probe compounds using public and commercial sources of chemical structures and the issues related to doing this type of analysis 27 . By organizing the data on small molecules tested against the Ebola virus similarly in a central database and using machine learning models based on public data may help identify additional compounds for testing. abstract: The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. url: https://doi.org/10.12688/f1000research.6120.1 doi: 10.12688/f1000research.6120.1 id: cord-328176-fck2ktxi author: Mahapatra, Manojkumar title: Methyl-2-arylidene hydrazinecarbodithioates: synthesis and biological activity date: 2013-02-19 words: 2398.0 sentences: 140.0 pages: flesch: 46.0 cache: ./cache/cord-328176-fck2ktxi.txt txt: ./txt/cord-328176-fck2ktxi.txt summary: This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC(50) value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation. It is interesting to note that preferably compounds with tridentate ligand characteristics (IIl, IIi, and IIc) showed potent anti-proliferative activity against the HL60 cells (Table 3 ). The compounds investigated are known as intermediates in the synthesis of many thiosemicarbazones but their usefulness as medicinally active agents has not yet been studied. abstract: Methyl-2-arylidene hydrazine-carbodithioate has not been of particular interest to researchers even though its metal complexes are extensively reported on due to their biological activity. This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC(50) value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. They were also most inhibitory to human embryonic lung (HEL) fibroblast proliferation (5.3 μM, 17 μM, and 2.6 μM). Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation. url: https://www.ncbi.nlm.nih.gov/pubmed/32214621/ doi: 10.2478/s11696-013-0346-4 id: cord-330465-16j5vm7h author: Marciniec, Krzysztof title: Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study date: 2020-08-05 words: 6908.0 sentences: 396.0 pages: flesch: 48.0 cache: ./cache/cord-330465-16j5vm7h.txt txt: ./txt/cord-330465-16j5vm7h.txt summary: The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC(50) (half maximal inhibitory concentration) equal to 0.02 μM. In order to check the potential toxic properties of the compounds 3-5, docking study of phosphate betulin derivatives to cellular proteins was carried out. According to the results of docking (Table S1 ) obtained from AutoDock Vina, four potential SARS-CoV-2 inhibitors (BVM, betulinic acid, and compounds 4 and 6) were selected based on a lower negative dock energy value. abstract: Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC(50) (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest. url: https://www.ncbi.nlm.nih.gov/pubmed/32764519/ doi: 10.3390/biom10081148 id: cord-327946-mqakaisa author: Massari, Serena title: Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase date: 2020-10-16 words: 3467.0 sentences: 205.0 pages: flesch: 48.0 cache: ./cache/cord-327946-mqakaisa.txt txt: ./txt/cord-327946-mqakaisa.txt summary: title: Synthesis and Characterization of 1,2,4-Triazolo[1,5-a]pyrimidine-2-carboxamide-based Compounds Targeting the PA-PB1 Interface of Influenza A Virus Polymerase In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide scaffolds. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. Finally, with the aim to gain information on how two different moieties, such as the cHTC and the 2-carbamoylphenyl, showed a favorable ability to disrupt PA-PB1 interaction, computational studies were performed to predict the binding mode of benzamide derivative 23 within the PA cavity with respect to hit compound 4. abstract: Influenza viruses (Flu) are responsible for seasonal epidemics causing high rates of morbidity, which can dramatically increase during severe pandemic outbreaks. Antiviral drugs are an indispensable weapon to treat infected people and reduce the impact on human health, nevertheless anti-Flu armamentarium still remains inadequate. In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide scaffolds. By merging these moieties, two very interesting hybrid compounds were recently identified, starting from which, in this paper, a series of analogues were designed and synthesized. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. For few compounds, the ability to efficiently inhibit PA-PB1 subunits interaction did not translate into anti-Flu activity. Chemical/physical properties were investigated for a couple of compounds suggesting that the low solubility of compound 14, due to a strong crystal lattice, may have impaired its antiviral activity. Finally, computational studies performed on compound 23, in which the phenyl ring suitably replaced the cycloheptathiophene, suggested that, in addition to hydrophobic interactions, H-bonds enhanced its binding within the PA(C) cavity. url: https://api.elsevier.com/content/article/pii/S0223523420309168 doi: 10.1016/j.ejmech.2020.112944 id: cord-259744-r9j5yzfc author: McDonagh, Phillip title: Identification and characterisation of small molecule inhibitors of feline coronavirus replication date: 2014-12-05 words: 5636.0 sentences: 258.0 pages: flesch: 41.0 cache: ./cache/cord-259744-r9j5yzfc.txt txt: ./txt/cord-259744-r9j5yzfc.txt summary: Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. This study identifies three compounds (chloroquine, mefloquine, and hexamethylene amiloride) demonstrating a marked inhibitory effect on FCoV replication in vitro by significant reductions in virus induced CPE and viral titres at low micromolar concentrations when present during the early stages of viral replication. This study has identified three compounds demonstrating marked in vitro inhibition of FCoV in an immortalised cell line at low micromolar concentrations, including the first demonstration of antiviral effects of mefloquine against a coronavirus. abstract: Feline infectious peritonitis (FIP), a feline coronavirus (FCoV) induced disease, is almost invariably fatal with median life expectancy measured in days. Current treatment options are, at best, palliative. The objectives of this study were to evaluate a panel of nineteen candidate compounds for antiviral activity against FCoV in vitro to determine viable candidates for therapy. A resazurin-based cytopathic effect inhibition assay, which detects viable cells through their reduction of the substrate resazurin to fluorescent resorufin, was developed for screening compounds for antiviral efficacy against FCoV. Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. Three compounds, chloroquine, mefloquine, and hexamethylene amiloride demonstrated marked inhibition of virus induced CPE at low micromolar concentrations. Orthogonal assays confirmed inhibition of CPE was associated with significant reductions in viral replication. Selectivity indices calculated based on in vitro cytotoxicity screening and reductions in extracellular viral titre were 217, 24, and 20 for chloroquine, mefloquine, and hexamethylene amiloride respectively. Preliminary experiments performed to inform the antiviral mechanism of the compounds demonstrated all three acted at an early stage of viral replication. These results suggest that these direct acting antiviral compounds, or their derivatives, warrant further investigation for clinical use in cats with FIP. url: https://www.sciencedirect.com/science/article/pii/S0378113514005082 doi: 10.1016/j.vetmic.2014.10.030 id: cord-301349-m4nr3pqx author: Mirza, Muhammad Usman title: Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach date: 2020-09-02 words: 7369.0 sentences: 370.0 pages: flesch: 46.0 cache: ./cache/cord-301349-m4nr3pqx.txt txt: ./txt/cord-301349-m4nr3pqx.txt summary: The aim of this study was to discover selective CCR5, CXCR4 and dual CCR5/CXCR4 antagonists based on both receptor-and ligand-based virtual screening methods together with molecular dynamics (MD) simulations and binding free energy calculations. The most promising compounds resulting from VS were evaluated for antiviral activity by a luciferase assay in TZM-bl cells infected with wild type HIV-1 strains NL4.3 (CXCR4-tropic strain, X4) and BaL (CCR5-tropic strain, R5). After a careful post-MD inspection, 43 compounds were selected based on the following criteria; (1) overall backbone stability of the protein/ligand complex, (2) electrostatic (ΔE ele ) and van der Waals (ΔE vdw ) interaction energy, (3) H-bonds occupancy, and (4) binding pocket residual contribution towards ligands. Compound 27, the most promising compound after receptor-based screening (IC 50 = 10.64 µM), showed a significant H-bond interaction profile with the residues lining the binding pocket of CCR5, as reported also for maraviroc [39, 80] . abstract: Chemokine receptors are key regulators of cell migration in terms of immunity and inflammation. Among these, CCR5 and CXCR4 play pivotal roles in cancer metastasis and HIV-1 transmission and infection. They act as essential co-receptors for HIV and furnish a route to the cell entry. In particular, inhibition of either CCR5 or CXCR4 leads very often the virus to shift to a more virulent dual-tropic strain. Therefore, dual receptor inhibition might improve the therapeutic strategies against HIV. In this study, we aimed to discover selective CCR5, CXCR4, and dual CCR5/CXCR4 antagonists using both receptor- and ligand-based computational methods. We employed this approach to fully incorporate the interaction attributes of the binding pocket together with molecular dynamics (MD) simulations and binding free energy calculations. The best hits were evaluated for their anti-HIV-1 activity against CXCR4- and CCR5-specific NL4.3 and BaL strains. Moreover, the Ca(2+) mobilization assay was used to evaluate their antagonistic activity. From the 27 tested compounds, three were identified as inhibitors: compounds 27 (CCR5), 6 (CXCR4) and 3 (dual) with IC(50) values ranging from 10.64 to 64.56 μM. The binding mode analysis suggests that the active compounds form a salt bridge with the glutamates and π-stacking interactions with the aromatic side chains binding site residues of the respective co-receptor. The presented hierarchical virtual screening approach provides essential aspects in identifying potential antagonists in terms of selectivity against a specific co-receptor. The compounds having multiple heterocyclic nitrogen atoms proved to be relatively more specific towards CXCR4 inhibition as compared to CCR5. The identified compounds serve as a starting point for further development of HIV entry inhibitors through synthesis and quantitative structure-activity relationship studies. url: https://www.sciencedirect.com/science/article/pii/S0928098720303250?v=s5 doi: 10.1016/j.ejps.2020.105537 id: cord-328834-yetnlb2j author: Mohsin, Noor ul Amin title: Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review date: 2020-06-15 words: 5675.0 sentences: 458.0 pages: flesch: 57.0 cache: ./cache/cord-328834-yetnlb2j.txt txt: ./txt/cord-328834-yetnlb2j.txt summary: Upon in vitro evaluation, compound 10 ( Fig. 3) showed prominent activity (87% growth inhibition) against colon cancer cell line (HCT-116) as compared to fluorouracil (67% inhibition). Derivatives bearing electron withdrawing groups at positions # 5, # 6 and # 7 of chromone scaffold showed better activity. Upon evaluation as anticancer agents by MTT assay, compounds 22 (IC 50 = 1.42 ± 0.13 mM) and 23 (IC 50 = 2.92 ± 0.94 mM) showed prominent in vitro activity versus breast cancer cell line (T47D) as compared to doxorubicin (IC 50 = 0.33 ± 0.05 mM). Incorporation of methyl and ethyl group in the heterocyclic ring showed comparable activity to unsubstituted derivatives [47] . Attachment of methyl group with chromone core also produced less active derivatives [51] . synthesized fluorine-containing chromone and tetrazole hybrid molecules by Ugi-azide reaction [63] These derivatives displayed moderate antimicrobial activity as is evident by compound 51 (MIC = 20 mg/mL) activity versus Pseudomonas aeruginosa (P. abstract: Chromone derivatives possess a spectrum of biological activities. Chromone has been recognized as a privileged structure for new drug invention and development. Substitution pattern of chromone scaffold determines different type of biological activities. The type, number and position of substituents connected to the chromone core play a vital role in determining pharmacological activities. In the present review, we have discussed new chromone derivatives as anticancer, anti-diabetic, antimicrobial, anti-inflammatory, antioxidant and as anti-Alzheimer agents. This review deals with the chromone derivatives prepared by combining chromone molecule with various natural and synthetic pharmacophores and pharmacological activities presented by them. The main aim is to highlight the diversified pharmacological activities exhibited by chromone hybrid molecules during the last eight to ten years. url: https://www.ncbi.nlm.nih.gov/pubmed/32836513/ doi: 10.1007/s11094-020-02187-x id: cord-264316-do0px1gq author: Mucha, Artur title: Metallo-aminopeptidase inhibitors date: 2010-05-10 words: 14674.0 sentences: 769.0 pages: flesch: 41.0 cache: ./cache/cord-264316-do0px1gq.txt txt: ./txt/cord-264316-do0px1gq.txt summary: This review focuses on the strict metallo-aminopeptidases because they constitute the largest and the most homogenous class of these enzymes and use one or two metal ions in their active sites to specifically release the N-terminal amino acid residues of polypeptides and proteins. Similar to other amino acid and peptide mimetics used as protease inhibitors, this is the effect of the incorporation of a covalent or non-covalent binding group (here involved in coordination of a catalytic metal ion(s) in the enzyme active site) into a substrate structure. Additionally, the P1 side chain of the aminophosphonic acid analogues (or more effectively, both P1 and P1 0 residues of the pseudopeptides phosphoryl moiety) gives further possibility of structural optimization of substituents interacting with the S1 and S1 0 binding pockets of the enzyme (Fig. 3) Fig. 4 ), appeared to be efficient inhibitors of LAP with a K i ¼ 0.15 [90] and 0.23 mM [87] for the R (L) enantiomers. abstract: Aminopeptidases are enzymes that selectively hydrolyze an amino acid residue from the N-terminus of proteins and peptides. They are important for the proper functioning of prokaryotic and eukaryotic cells, but very often are central players in the devastating human diseases like cancer, malaria and diabetes. The largest aminopeptidase group include enzymes containing metal ion(s) in their active centers, which often determines the type of inhibitors that are the most suitable for them. Effective ligands mostly bind in a non-covalent mode by forming complexes with the metal ion(s). Here, we present several approaches for the design of inhibitors for metallo-aminopeptidases. The optimized structures should be considered as potential leads in the drug discovery process against endogenous and infectious diseases. url: https://www.sciencedirect.com/science/article/pii/S0300908410001768 doi: 10.1016/j.biochi.2010.04.026 id: cord-329078-gnnis7pl author: Musella, Simona title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor date: 2016-11-29 words: 3935.0 sentences: 215.0 pages: flesch: 48.0 cache: ./cache/cord-329078-gnnis7pl.txt txt: ./txt/cord-329078-gnnis7pl.txt summary: title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor Tryptamine derivative 17a was found to have a selective inhibitory activity against human varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. Arbidol [34] and delavirdine [35] , are examples of marketed indole-containing antiviral drugs, whereas Panobinostat (LBH589) [36] , being a HDAC (histone deacetylase) inhibitor, is actively undergoing clinical evaluation against human immunodeficiency virus (HIV) type 1 (See Fig. 1 ). The antiviral activity was expressed as EC50, being the compound concentration required to reduce virus-plaque formation (VZV) by 50%. The mixture was stirred for 3 h at room temperature, then was washed with water (3 Â 50 mL), dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using DCM/MeOH (9:1 v/v) as mobile phase. 4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus abstract: We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the indole nucleus. Modifications of this template through Mannich and Friedel-Crafts reactions, coupled with nucleophilic displacement and reductive aminations led to 23 final derivatives, which were pharmacologically tested. Tryptamine derivative 17a was found to have a selective inhibitory activity against human varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. A structure-activity relationship (SAR) study showed that the presence of a biphenyl ethyl moiety and the acetylation at the amino group of tryptamine are a prerequisite for anti-VZV activity. The novel compound shows the same activity against thymidine kinase (TK)-competent (TK(+)) and TK-deficient (TK(−)) VZV strains, pointing to a novel mechanism of antiviral action. url: https://api.elsevier.com/content/article/pii/S0223523416307401 doi: 10.1016/j.ejmech.2016.09.014 id: cord-003341-z5w56zeq author: Nguyen, Thi Thanh Hanh title: In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4 date: 2013-12-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3(pro)) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). Thirty-six compounds were selected for in vitro assay against NS2B-NS3(pro) expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC(50) values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3(pro) inhibitors were further confirmed as competitive inhibitors with K(i) values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3(pro) active site with inhibition compounds were also identified. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269914/ doi: 10.3390/molecules181215600 id: cord-021419-nypnib0h author: Olsufyeva, Evgenia N. title: Main trends in the design of semi-synthetic antibiotics of a new generation date: 2020-03-17 words: 16144.0 sentences: 923.0 pages: flesch: 45.0 cache: ./cache/cord-021419-nypnib0h.txt txt: ./txt/cord-021419-nypnib0h.txt summary: In this review, the following classes of compounds are considered as scaffolds for the synthesis of new antibiotics: polycyclic glycopeptides of the vancomycin ± teicoplanin group, classical macrolides, macrolides of the amphotericin B ± oligomycin group, anthracyclines, aureolic acid derivatives, heliomycin, synthetic benzoxaboroles and some other antibiotics. 42 Antibacterial activity of derivatives 52 ± 55 modified at the C(11)7OH group of the aglycone was evaluated compared to the starting antibiotics vancomycin (1) and azithromycin (30) on a panel of Gram-positive and Gramnegative bacterial strains (8 and 3 strains, respectively). In order to improve antifungal properties, cytotoxic and therapeutic characteristics and to study the mechanisms of action, series of new semi-synthetic derivatives based on AmB (63a) and bioengineered analogues S44HP (64a), BSG005 (65a), BSG022 (66a), BSG019 (67), BSG003 (68a) and BSG018 (69) were synthesized (in collaboration with the company BIOSERGEN, Norway) (Scheme 17). abstract: This review summarizes main advances achieved by Russian researchers in the synthesis and characterization of semi-synthetic antibiotics of a new generation in the period from 2004 to 2019. The following classes of compounds are considered as the basis for modification: polycyclic antibacterial glycopeptides of the vancomycin group, classical macrolides, antifungal polyene macrolides, the antitumour antibiotic olivomycin A, antitumour anthracyclines and broad-spectrum antibiotics, in particular, oligomycin A, heliomycin and some other. Main trends in the design of modern anti-infective and antitumour agents over this period are considered in relation to original natural antibiotics, which have been independently discovered by Russian researchers. It is shown that a new type of hybrid structures can, in principle, be synthesized based on glycopeptides, macrolides and other antibiotics, including heterodimers containing a new benzoxaborole pharmacophore. The review addresses the influence of the length of the spacer between two antibiotic molecules on the biological activity of hybrid structures. A combination of genetic engineering techniques and methods of organic synthesis is shown to be useful for the design of new potent antifungal antibiotics based on polyenes of the amphotericin B group. Many new semi-synthetic analogues exhibit important biological properties, such as a broad spectrum of activity and low toxicity. Emphasis is given to certain aspects related to investigation of a broad range of biological activity and mechanisms of action of new derivatives. The bibliography includes 101 references. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149660/ doi: 10.1070/rcr4892 id: cord-000445-2x7dfl1q author: Paliwal, Sarvesh K. title: Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances date: 2011-05-10 words: 8603.0 sentences: 401.0 pages: flesch: 44.0 cache: ./cache/cord-000445-2x7dfl1q.txt txt: ./txt/cord-000445-2x7dfl1q.txt summary: brucei rhodesiense than the corresponding 2,5-substituted isomers (compounds 1-10, figure 4a), while among the 2, 5-substituted dications, the compounds possessing cationic substituents adjacent to nitrogen atoms in pyridine rings displayed superior activities against parasites compared to pentamidine as evident from compound 6 (figure 4b) which showed promising anti-trypanosomal activity (0.001µM) and lower cytotoxicity (4.90µM) than pentamidine and melarsoprol, but had poor in vivo activity giving only 1/4 cures in the STIB900 mouse model. Structure of two phenylbenzofuran dications with promising anti-trypanosomal activity Tidwell RR et al found that the in vitro anti-trypanosomal activities of bisbenzofuran derivatives against Trypanosoma brucei rhodesiense, and cytotoxicity against mammalian cells depended on the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. Thus promising in vitro, anti-trypanosomal activity, excellent potency in the acute mouse model of trypanosomiasis and the reduced cytotoxicity (1.9 µM) of compound 1 compared to pentamidine warrants further pre-clinical and clinical trials of this molecule. abstract: Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163371/ doi: 10.3797/scipharm.1012-08 id: cord-323093-u3ozc9ry author: Rathnayake, Athri D. title: 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date: 2020-08-19 words: 7158.0 sentences: 362.0 pages: flesch: 56.0 cache: ./cache/cord-323093-u3ozc9ry.txt txt: ./txt/cord-323093-u3ozc9ry.txt summary: After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection. abstract: Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32747425/ doi: 10.1126/scitranslmed.abc5332 id: cord-277802-f8pyn3rx author: Roman, Gheorghe title: Mannich bases in medicinal chemistry and drug design date: 2015-01-07 words: 53972.0 sentences: 2237.0 pages: flesch: 41.0 cache: ./cache/cord-277802-f8pyn3rx.txt txt: ./txt/cord-277802-f8pyn3rx.txt summary: Aminomethylated derivatives of hydroxycarbazoles have been also mentioned in a different study [60] , which described the synthesis of a small series of phenolic Mannich bases 47 (Fig. 8 ) obtained from 5-substituted 2-hydroxy-5H-benzo[b]carbazole-6,11-diones along with their in vitro anticancer evaluation at National Cancer Institute (NCI) using an in-house developed screening panel of approximately 60 cell lines derived from nine different types of cancer. Recently, Mannich bases 132 ( Fig. 24 ) obtained using Schiff bases derived from 5-fluoroisatin and 4-arylideneaminoanilines as substrates and ciprofloxacin as amine reagent were shown to be generally less potent antibacterials than reference drug ciprofloxacin, although some candidates had MIC values comparable to those of ciprofloxacin against the investigated bacteria [164] . Both types of Mannich bases 133l and 134l, featuring a 1,2,4-triazole moiety at position 5 of the triazolethione scaffold, showed good antibacterial activity, but compounds 134l were generally more potent than 133l, and two of candidates 134l actually had MIC values comparable to those of reference drug ciprofloxacin [177] . abstract: The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors. url: https://www.ncbi.nlm.nih.gov/pubmed/25462280/ doi: 10.1016/j.ejmech.2014.10.076 id: cord-300872-blycbi4u author: Saadeh, Haythem A. title: Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines date: 2020-09-21 words: 16077.0 sentences: 768.0 pages: flesch: 44.0 cache: ./cache/cord-300872-blycbi4u.txt txt: ./txt/cord-300872-blycbi4u.txt summary: Some of these strains have even become resistant to many antibiotics and chemotherapeutic agents; These prepared compounds were subjected to bioactivity screening against the highly pathogenic H5N1 avian influenza viruses, with the results expressed as percentages of growth inhibition, and to cytotoxicity evaluation against the A549 cell line. A synthetic procedure (Scheme 13) involved a condensation reaction between the amino group (NH2) in 49 and the carbonyl group in salicylic aldehyde (50), followed by intramolecular cyclization under a These prepared compounds were screened for potential anticancer activity against MCF-7, HCT 116, HepG-2, and A549 using the MMT assay. This compound was screened against MCF-7 and Hela cancer cell lines using MMT assay, giving IC50 values of 21.02 and 27.73 mM, respectively In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives (Scheme 14) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [36] . abstract: Compounds containing the 8-hydroxyquinoline (8-HQ) 1 nucleus exhibit a wide range of biological activities, including antimicrobial, anticancer, and antifungal effects. The chemistry and biology of this group have attracted the attention of chemists, medicinal chemists, and professionals in health sciences. A number of prescribed drugs incorporate this group, and numerous 8-HQ- based molecules can be used to develop potent lead compounds with good efficacy and low toxicity. This review focusses on the recent advances in the synthesis of 8-HQ derivatives with different pharmacological properties, including anticancer, antiviral, and antibacterial activities. For this purpose, recent relevant references were searched in different known databases and search engines, such as MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, Scientific Information Database (SID), SciFinder, and Institute for Scientific Information (ISI) Web of Knowledge. This review article provides a literature overview of the various synthetic strategies and biological activities of 8-HQ derivatives and covers the recent related literature. Taken together, compounds containing the 8-HQ moiety have huge therapeutic value and can act as potential building blocks for various pharmacologically active scaffolds. In addition, several described compounds in this review could act leads for the development of drugs against numerous diseases including cancer. url: https://doi.org/10.3390/molecules25184321 doi: 10.3390/molecules25184321 id: cord-025119-201ac32t author: Salman, Saad title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 words: 3144.0 sentences: 162.0 pages: flesch: 37.0 cache: ./cache/cord-025119-201ac32t.txt txt: ./txt/cord-025119-201ac32t.txt summary: Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Here, we analyzed different medicinal compounds using a virtual screening method to obtain promising inhibitors for these viral proteins that could be further utilized for SARS-COV-2 treatment. More than 300 medicinal compounds with immunomodulatory and antiviral activity were added to the Raccoon2 plugin of Autodock vina to perform virtual screening to obtain promising inhibitors for SARS-COV-2 proteins. This study aimed to obtain novel drug candidates that have the capability to interact with the active site of all of these viral proteins and should possess efficient pharmacokinetic profile with low toxicity to ensure safety during administration. • Docking interaction of immunomodulatory medicinal compounds library filtered six promising medicinal compounds against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) viral proteins. abstract: Aim: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a pernicious viral disease, causes acute respiratory distress responsible for mortality and morbidity worldwide. To screen different immunomodulatory medicinal compounds to unravel their interaction with SARS-COV-2 viral proteins. Materials & methods: A library of immunomodulatory medicinal compounds with antiviral capability were analyzed against SARS proteases, spike protein and nonstructural proteins (NSP-9, 15) using Autodock vina. Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Further ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis showed good pharmacokinetic properties and low acute toxicity of these compounds. Conclusion: The current study provides convincing evidence that these medicinal compounds exert antiviral activity against the SARS-COV-2 virus and could be further exploited for the treatment of this disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243912/ doi: 10.2217/fvl-2020-0079 id: cord-024652-4i6kktl0 author: Santra, Hiran Kanti title: Natural Products as Fungicide and Their Role in Crop Protection date: 2020-05-12 words: 20643.0 sentences: 1184.0 pages: flesch: 39.0 cache: ./cache/cord-024652-4i6kktl0.txt txt: ./txt/cord-024652-4i6kktl0.txt summary: A large number of bioactive compounds ranging from direct plant (both cryptogams algae and moss and phanerogams)-derived natural extracts, essential oil of aromatic plants, and low-molecular-weight antimicrobial compounds known as phytoalexins to secondary metabolites that are both volatile and nonvolatile organic compounds of microbes (fungal and actinobacterial members) residing inside the host tissue, called endophyte, are widely used as agricultural bioweapons. Endophytic culture extracts are also known to be rich sources of phenolics; usually they are directly proportional to the antioxidative property of any fungal isolate, but in some particular cases, they are characterized with their antifungal potentials against phytopathogenic fungus. So it is a great opportunity to use the unique mixture of volatile organic compounds of the endophytic isolate to reduce the crop loss caused by the pathogenic infection on the commercially valuable plant of cherry tomato worldwide. abstract: Seeking solutions from nature for solving one and all problems is the age-old practice for mankind, and natural products are proved to be the most effective one for keeping up the balance of development as well as the “healthy, wealthy, and well” condition of mother nature. Fungal pathogens are proved to be a common and popular contaminant of agroecosystem that approximately causes 70–80% of total microbial crop loss. To meet the proper global increasing need of food products as a result of population explosion, managing agricultural system in an eco-friendly and profitable manner is the prime target; thus the word “sustainable agriculture” plays it part, and this package is highly effective when coupled with nature-derived fungicidal products that can minimize the event of fungal infections in agrarian ecosystem. Present study enlists the most common and effective natural products that might be of plant or microbial origin, their mode of action, day-by-day development of phytopathogenic resistance against the prevailing fungicides, and also their role in maintenance of sustainability of agricultural practices with special emphasis on their acceptance over the synthetic or chemical one. A large number of bioactive compounds ranging from direct plant (both cryptogams algae and moss and phanerogams)-derived natural extracts, essential oil of aromatic plants, and low-molecular-weight antimicrobial compounds known as phytoalexins to secondary metabolites that are both volatile and nonvolatile organic compounds of microbes (fungal and actinobacterial members) residing inside the host tissue, called endophyte, are widely used as agricultural bioweapons. The rhizospheric partners of plant, mycorrhizae, are also a prime agent of this chemical warfare and protect their green partners from fungal invaders and emphasize the concept of “sustainable agriculture.” url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212785/ doi: 10.1007/978-981-15-3024-1_9 id: cord-283128-9mbi75de author: Singh, Ramendra K. title: Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid date: 2009-12-09 words: 4164.0 sentences: 211.0 pages: flesch: 57.0 cache: ./cache/cord-283128-9mbi75de.txt txt: ./txt/cord-283128-9mbi75de.txt summary: The resulting product, dissolved in anhydrous pyridine, was added dropwise to the activated folate 5 in 1:1 molar proportion in the presence of DCC and DMAP to yield the compound 10 in 26% (Scheme 4). The molecules 2, 3, 4, 6 and 8 have shown remarkable antibacterial activities with MIC ranging between 0.09 and 0.67 mM (in vitro) against gram-positive cocci (Streptococcus virudans) as well as gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Proteus mirabeilis) bacterial strains. The compound 7, dissolved in dry pyridine (5 ml), was added dropwise to the activated folate ester 5 (286 mg, 0.51 mmol) and stirred the reaction mixture for 15 min. Compound 9 (100 mg, 0.24 mmol), dissolved in dry pyridine (6 ml), was added dropwise to the activated ester 5 (157 mg, 0.28 mmol), stirred the reaction mixture for 20 min and TEA (0.5 ml), DCC (123 mg, 0.6 mmol) and DMAP (32 mg) were further added. abstract: Curcumin bioconjugates, viz. di-O-tryptophanylphenylalanine curcumin (2), di-O-decanoyl curcumin (3), di-O-pamitoyl curcumin (4), di-O-bis-(γ,γ)folyl curcumin (6), C(4)-ethyl-O-γ-folyl curcumin (8) and 4-O-ethyl-O-γ-folyl curcumin (10) have been synthesized and tested for their antibacterial and antiviral activities. The conjugates 2, 3, 4, 6 and 8 have shown very promising antibacterial activity with MIC ranging between 0.09 and 0.67 μM against Gram-positive cocci and Gram-negative bacilli. Further, the conjugates 2, 3, 6, 8 and 10 have been screened for their antiviral activities against HSV, VSV, FIPV, PIV-3, RSV and FHV and the molecules 2 and 3 have shown good results with EC(50) 0.011 μM and 0.029 μM against VSV and FIPV/FHV, respectively. However, the molecules did not show expected results against HIV-1 III(B) and ROD strains in MTT assay. url: https://doi.org/10.1016/j.ejmech.2009.12.002 doi: 10.1016/j.ejmech.2009.12.002 id: cord-323479-vlgv3nwq author: Speranza, Jasmine title: Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies date: 2020-03-01 words: 14357.0 sentences: 712.0 pages: flesch: 42.0 cache: ./cache/cord-323479-vlgv3nwq.txt txt: ./txt/cord-323479-vlgv3nwq.txt summary: tinctoria has been thoroughly investigated and the plant was proven to contain many valuable biologically active compounds, including several alkaloids, among which tryptanthrin, indirubin, indolinone, phenolic compounds, and polysaccharides as well as glucosinolates, carotenoids, volatile constituents, and fatty acids. In the lyophilized extracts'' analysis, beyond the characterization and quantification of 122 compounds previously described, the following indole derivatives were described for the first time: acetylindican, malonylindican, two Another important compound of this class is tryptanthrin, indolo-[2,1-b]-quinazoline alkaloid ( Figure 4 ), which is also responsible for some biological activities of I. In particular, the study concerned the evaluation of anti-microbial activity of fractions obtained from different parts of the plant (branches, flowers, leaves, and roots) by extraction with 14 different solvents, which was performed using a micro-titer plate method against seven bacterial and four fungal strains. Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin abstract: Isatis tinctoria L. (Brassicaceae), which is commonly known as woad, is a species with an ancient and well-documented history as an indigo dye and medicinal plant. Currently, I. tinctoria is utilized more often as medicinal remedy and also as a cosmetic ingredient. In 2011, I. tinctoria root was accepted in the official European phytotherapy by introducing its monograph in the European Pharmacopoeia. The biological properties of raw material have been known from Traditional Chinese Medicine (TCM). Over recent decades, I. tinctoria has been investigated both from a phytochemical and a biological point of view. The modern in vitro and in vivo scientific studies proved anti-inflammatory, anti-tumour, antimicrobial, antiviral, analgesic, and antioxidant activities. The phytochemical composition of I. tinctoria has been thoroughly investigated and the plant was proven to contain many valuable biologically active compounds, including several alkaloids, among which tryptanthrin, indirubin, indolinone, phenolic compounds, and polysaccharides as well as glucosinolates, carotenoids, volatile constituents, and fatty acids. This article provides a general botanical and ethnobotanical overview that summarizes the up-to-date knowledge on the phytochemistry and biological properties of this valuable plant in order to support its therapeutic potential. Moreover, the biotechnological studies on I. tinctoria, which mainly focused on hairy root cultures for the enhanced production of flavonoids and alkaloids as well as on the establishment of shoot cultures and micropropagation protocols, were reviewed. They provide input for future research prospects. url: https://doi.org/10.3390/plants9030298 doi: 10.3390/plants9030298 id: cord-016425-8yd2bkf1 author: Strobel, Gary title: Novel Natural Products From Rainforest Endophytes date: 2005 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Endophytic microorganisms are found in virtually every higher plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to pathogenic. Endophytes may contribute to their host plant by producing a plethora of substances that provide protection and survival value to the plant. Ultimately, these compounds, once isolated and characterized, may also have potential for use in modern medicine. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation and culturing of individual endophytes followed by purification and characterization of some of their natural products. The potential of finding new drugs that may be effective candidates for treating newly developing diseases in humans is great. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120694/ doi: 10.1007/978-1-59259-976-9_15 id: cord-318854-xaus3bma author: Sun, Yi title: Chapter 4 Bioactivity and Synthesis of Diarylheptanoids From Alpinia officinarum date: 2016-12-31 words: 5322.0 sentences: 298.0 pages: flesch: 48.0 cache: ./cache/cord-318854-xaus3bma.txt txt: ./txt/cord-318854-xaus3bma.txt summary: In this review, we discuss the antitumor-promoting, antiinflammatory, cytotoxic, antimicrobial, antiinfluenza, and antiherpes simplex-1 virus activities of diarylheptanoids isolated from galangal resulting from our own and other research groups'' investigation. Compound 6 showed the strongest activity among the four diarylheptanoids (IC 50 : 10 μM), and it also inhibited the mRNA expression of tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2, as well as protein levels of microphthalmia-associated transcription factor (MITF) [52] . Compounds 2, 6, 15, 16, 47, and 48 were tested for their inhibitory effects on NO production in the LPS-activated macrophage cell line RAW 264.7 [15] . Thus, the reports cited above suggest that diarylheptanoids possess inhibitory effects against inflammatory and tumor-promoting activities. Compound 4 was also active against influenza virus with an EC 50 value of <10 μg/mL [61] , which suggests that 4 is an effective diarylheptanoid against both RSV and influenza virus in vitro. abstract: Abstract Many diarylheptanoids were isolated from the galangal (rhizome of Alpinia officinarum). We are reported the antitumor-promoting, antiinflammatory, cytotoxic, antiinfluenza virus, and antiherpes simplex-1 virus activities of diarylheptanoids. These components in our dietary and herbal supplements are considered to be relatively nontoxic to human. In addition, we synthesized the new compounds. In this review, we discuss the antitumor-promoting, antiinflammatory, cytotoxic, antimicrobial, antiinfluenza, and antiherpes simplex-1 virus activities of diarylheptanoids isolated from galangal resulting from our own and other research groups' investigation. url: https://www.sciencedirect.com/science/article/pii/B9780444636010000041 doi: 10.1016/b978-0-444-63601-0.00004-1 id: cord-260014-q5sug7uu author: Szűcs, Zsolt title: Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity date: 2020-06-29 words: 5179.0 sentences: 333.0 pages: flesch: 51.0 cache: ./cache/cord-260014-q5sug7uu.txt txt: ./txt/cord-260014-q5sug7uu.txt summary: We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. On the other hand, this result is in line with our previous findings on ristocetin and teicoplanin aglycone derivatives, indicating that even minor structural differences in the peptide core can lead to significantly different anti-influenza virus activity [27] . On the other hand, this result is in line with our previous findings on ristocetin and teicoplanin aglycone derivatives, indicating that even minor structural differences in the peptide core can lead to significantly different anti-influenza virus activity [27] . Hence, we established, by virus yield assays, that compound 6 suppresses the replication of influenza virus and coronavirus, and for the other viruses, activity was indicated by the protection against viral CPE. Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: An aggregation and receptor binding study abstract: Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index. url: https://www.ncbi.nlm.nih.gov/pubmed/32610683/ doi: 10.3390/ph13070139 id: cord-306934-29ljbl7g author: Tonelli, Michele title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives date: 2009-07-01 words: 8526.0 sentences: 442.0 pages: flesch: 58.0 cache: ./cache/cord-306934-29ljbl7g.txt txt: ./txt/cord-306934-29ljbl7g.txt summary: Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. First of all, the binding site identified by our procedure is very close to the putative binding site proposed for two allosteric inhibitors of BVDV RdRp, VP32947 and BPIP, 23 Table 5 Cytotoxicity against MT-4, MDBK, BHK and Vero-76 cell lines and YFV, Reo-1, CVB-2, RSV, HSV-1 and Sb-1 inhibitory activity of triazene derivatives of structure F and G Tables 3 and 4. In view of these considerations, molecular modeling investigations were performed to study wether the active compounds of structures A-C could target the BVDV RNA-dependent RNA-polymerase (RdRp), which shares some structural similarity with HCV RdRp. Indeed a good agreement was observed between the trend exhibited by the IC 50 (calculated from the estimated free energies of binding) and the corresponding biological activities determined for these compounds in BVDV infected MDBK cell line. abstract: Abstract Twelve aminoarylazocompounds (A–C) and 46 aryltriazene 7 derivatives (D–G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1 > 7 > 8 > 4; YFV: 7 > 5; CVB-2: 25 > 56 > 18; RSV: 14 > 20 > 55 > 38 > 18 > 19; HSV-1: 2. For these compounds the EC50 ranged from 1.6μM (1) to 12μM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values. url: https://www.ncbi.nlm.nih.gov/pubmed/19482481/ doi: 10.1016/j.bmc.2009.05.020 id: cord-340331-51yq1rdo author: Tonelli, Michele title: Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus date: 2017-07-28 words: 6160.0 sentences: 285.0 pages: flesch: 42.0 cache: ./cache/cord-340331-51yq1rdo.txt txt: ./txt/cord-340331-51yq1rdo.txt summary: We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. The compounds, object of the present study, are characterized by the 1-aryl-4,6-diamino-1,2-dihydrotriazine scaffold, such as the cited cycloguanil, which was identified by us as prototype (1) of a new class of antiviral agents exploiting a host DHFR inhibition mechanism. Since host cell DHFR inhibition seemed the plausible explanation for the observed antiviral effect, we performed a combination experiment in which RSV-infected HeLa cells were exposed to compound 14 in combination with different concentrations of the natural DHFR substrate dihydrofolic acid ( reaction has a much higher impact on virus replication than on cell growth, which concurs with the promising antiviral selectivity of our host-directed DHFR inhibitors. The interesting dual activity of the 1-aryl-4,6-diamino-1,2dihydrotriazines against influenza and respiratory syncytial viruses, via inhibition of the cellular (human) DHFR enzyme, points to this host factor as a new therapeutic target for these two respiratory viruses. abstract: We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. Most analogues proved active against influenza B virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC(50) = 0.060 μM), and markedly exceeded (up to 327 times) the antiviral efficacy of ribavirin. Activity was also observed for two influenza A strains, including a virus with the S31N mutant form of M2 proton channel, which is the most prevalent resistance mutation for amantadine. Importantly, the compounds displayed nanomolar activity against RSV and a superior selectivity index, since the ratio of cytotoxic to antiviral concentration was >10,000 for the three most active compounds 11, 14 and 16 (EC(50) ∼0.008 μM), far surpassing the potency and safety profile of the licensed drug ribavirin (EC(50) = 5.8 μM, SI > 43). url: https://doi.org/10.1016/j.ejmech.2017.04.070 doi: 10.1016/j.ejmech.2017.04.070 id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 words: 8193.0 sentences: 522.0 pages: flesch: 46.0 cache: ./cache/cord-338436-0z828org.txt txt: ./txt/cord-338436-0z828org.txt summary: Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. abstract: Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development. url: https://www.ncbi.nlm.nih.gov/pubmed/32916958/ doi: 10.3390/v12091006 id: cord-017041-0zxoq68m author: Volochnyuk, Dmitriy M. title: Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry date: 2014-06-13 words: 16251.0 sentences: 955.0 pages: flesch: 47.0 cache: ./cache/cord-017041-0zxoq68m.txt txt: ./txt/cord-017041-0zxoq68m.txt summary: Herein we give a comprehensive review on the biological activity and synthesis of fluorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry. Herein we give a comprehensive review on the biological activity and synthesis of fl uorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry. In an alternative approach, Fluorouracil was prepared by direct fl uorination of different pyrimidine derivatives, including uracil [ 15 ] , cytosine [ 16 ] , and orotic acid [ 17 ] . Early synthesis of Floxuridine commenced from Fluorouracil ( 1 ) which was transformed into its mercury salt 28 and then allowed to react with 2-deoxy-Dribofuranosyl chloride derivative 29 (Scheme 4 ) [ 18 ] . More precisely, Trifl uridine is transformed into α,α,α-trifl uorothymidine monophosphate ( 76 ) by thymidine kinase (Scheme 21 ); similarly to the Fluorouracil derivatives discussed in the previous sections, compound 76 is true inhibitor of thymidylate synthase. abstract: The combination of a fluorine atom and a diazine ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated biologically active agents. Herein we give a comprehensive review on the biological activity and synthesis of fluorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121506/ doi: 10.1007/978-3-319-04435-4_7 id: cord-254036-0karwgz2 author: Wang, Runming title: Bismuth: Environmental Pollution and Health Effects date: 2019-09-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although it has been used for centuries, bismuth remains one of the least understood elements in the periodic table. Metallic bismuth and bismuth compounds have been widely used in the manufacture of alloys, pigments, cosmetics, and pharmaceuticals. As a “green” heavy metal, the substitution of lead with bismuth in some industries may partially resolve the environmental problems related to heavy metal pollution. In health care, as bismuth has low toxicity to humans, bismuth-based drugs such as colloidal bismuth subcitrate (CBS), ranitidine bismuth citrate (RBC), bismuth subsalicylate (BSS), bismuth iodoform and radioactive bismuth ((212)Bi/(213)Bi) complexes have been developed and used in clinics to treat various diseases. In most cases, bismuth therapies exhibit high therapeutic efficacies and little side effects; nevertheless, there are still reported cases of bismuth toxicity caused by bismuth over-dosage. url: https://www.sciencedirect.com/science/article/pii/B9780124095489118706 doi: 10.1016/b978-0-12-409548-9.11870-6 id: cord-326922-bajpr5a2 author: Watson, C. James title: Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors date: 2020-11-02 words: 7095.0 sentences: 417.0 pages: flesch: 38.0 cache: ./cache/cord-326922-bajpr5a2.txt txt: ./txt/cord-326922-bajpr5a2.txt summary: In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA''s Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] . abstract: INTRODUCTION: Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. METHODS: We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration “Drug Alerts and Statements” repository. We categorized reports into errors of “contamination,” suprapotency,” and “subpotency.” Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. RESULTS: We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. DISCUSSION: Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. CONCLUSION: In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards. url: https://www.ncbi.nlm.nih.gov/pubmed/33140232/ doi: 10.1007/s13181-020-00814-3 id: cord-021013-xvc791wx author: Wink, Michael title: Chapter 1 Allelochemical Properties or the Raison D'être of Alkaloids date: 2008-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter provides evidence that alkaloids are not waste products or functionless molecules as formerly assumed, but rather defense compounds employed by plants for survival against herbivores and against microorganisms and competing plants. These molecules were developed during evolution through natural selection in that they fit many important molecular targets, often receptors, of cells, which are seen in molecules that mimic endogenous neurotransmitters. The chapter discusses that microorganisms and herbivores rely on plants as a food source. Since both have survived, there must be mechanisms of adaptations toward the defensive chemistry of plants. Many herbivores have evolved strategies to avoid the extremely toxic plants and prefer the less toxic ones. Many herbivores have potent mechanisms to detoxify xenobiotics, which allow the exploitation of at least the less toxic plants. In insects, many specialists evolved that are adapted to the defense chemicals of their host plant, in that they accumulate these compounds and exploit them for their own defense. Alkaloids function as defense molecules against insect predators in the examples studied, and this is further support for the hypothesis that the same compound also serves for chemical defense in the host plant. It needs more experimental data to understand fully the intricate interconnections between plants, their alkaloids, and herbivores, microorganisms, and other plants. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148816/ doi: 10.1016/s0099-9598(08)60134-0 id: cord-012773-wtgk2d68 author: Xu, Ming-ming title: Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein date: 2019-10-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson’s disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as other damage, leading to neuronal death and eventually neurodegeneration. Early diagnosis and treatments targeting PD pathogenesis are urgently needed. Given its critical role in PD, α-syn is an attractive target for the development of both diagnostic tools and effective therapeutics. This review summarizes the progress toward discovering imaging probes and aggregation inhibitors for α-syn. Relevant strategies and techniques in the discovery of α-syn-targeted drugs are also discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470848/ doi: 10.1038/s41401-019-0304-y id: cord-003539-tazd6dvm author: Yang, Kun title: Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration date: 2019-03-02 words: 9249.0 sentences: 483.0 pages: flesch: 51.0 cache: ./cache/cord-003539-tazd6dvm.txt txt: ./txt/cord-003539-tazd6dvm.txt summary: According to the general procedure A, compound 2 was treated with 1-(Boc-amino)cyclopropanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3k: Yellow solid; yield, 28%; 1 H-NMR δ 11.96 (brs, 1H), 8 189.28, 180.10, 169.83, 164.69, 164.22, 161.39, 148.39, 134.15, 132.07, 123.98, 120.37, 112.73, 109.54, 107.67, 106.74, 66.57, 63.78 1-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)cyclobutan-aminium 2,2,2-trifluoroacetate (3l). According to the general procedure A, compound 2 was treated with 1-(Boc-amino)cyclobutanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3l: Yellow solid; yield, 28%; 1 H-NMR δ 11.95 (brs, 1H), 8 3-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)oxetan-3-aminium 2,2,2-trifluoroacetate (3m). According to the general procedure A, compound 2 was treated with 3-Boc-amino-3-oxetanecarboxylic acid and then purified by reverse phase flash chromatography to give compound 3m: Yellow solid; yield, 37%; 1 H-NMR δ 11.97 (brs, 2H), 8 1-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)cyclopentan-aminium 2,2,2-trifluoroacetate (3n). abstract: Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC(50)) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC(50) = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429262/ doi: 10.3390/molecules24050884 id: cord-261366-mtcalbo5 author: da Rosa Guimarães, Tatiana title: Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae) date: 2013-10-29 words: 4824.0 sentences: 269.0 pages: flesch: 54.0 cache: ./cache/cord-261366-mtcalbo5.txt txt: ./txt/cord-261366-mtcalbo5.txt summary: The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. In a previous screening of the anti-infective potential of marine invertebrates and seaweeds [28] , we observed a promising activity for the n-butanol fraction (BF) obtained from the ethanolic crude extract of this sponge that led us to perform this study. As it is important to understand the targets and the mode of action of a potential useful new antiviral agent, a set of experiments was carried out to determine the stages at which the most active samples (TSH fraction and compounds 1 and 2) affect the viral replication cycle. abstract: The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2. url: https://www.ncbi.nlm.nih.gov/pubmed/24172213/ doi: 10.3390/md11114176 id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 words: 46663.0 sentences: 2181.0 pages: flesch: 44.0 cache: ./cache/cord-020010-q58x6xb0.txt txt: ./txt/cord-020010-q58x6xb0.txt summary: In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133865/ doi: 10.1016/j.antiviral.2006.02.001 id: cord-023284-i0ecxgus author: nan title: Abstracts of publications related to QASR date: 2006-09-19 words: 19803.0 sentences: 1320.0 pages: flesch: 48.0 cache: ./cache/cord-023284-i0ecxgus.txt txt: ./txt/cord-023284-i0ecxgus.txt summary: Results: Methods developed for the investigation for the relationships between structure and toxic effects of compounds are summarized: a) The extra-thermodynamic approach: the Hansch paradigm, physical chemical properties that influence biological activity and their parametrization, originality of the Hansch approach, receptors and pharmacophores: the natural content of the Hansch approach, predictive value of QSARs, a statistifa1 tool: multiple linear regression analysis, the problem of correlations among molecular descriptors, other mathematical utilizations of extrathermodynamic parameters; b) The substructural approach: when topological (substructural) descriptors are needed, how to use topological decriptors; c) QSAR in mutagenicity and carcinogenicity: general problems, specific versions of the substructural approach used for mutagenicity and carcinogenicity, applications to mutagenicity and carcinogenicity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168536/ doi: 10.1002/qsar.19900090309 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel