Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 70 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 9524 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 48 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 70 compound 16 activity 9 figure 9 cell 9 SARS 9 Fig 7 virus 5 Synthesis 4 scheme 4 plant 4 antiviral 3 inhibitor 3 effect 3 derivative 3 COVID-19 2 table 2 study 2 structure 2 product 2 model 2 isolate 2 gram 2 fungus 2 extract 2 acid 2 Table 2 RNA 2 QSAR 2 MERS 2 HIV-1 2 HIV 2 HCV 2 Boc 1 wound 1 virtual 1 trypanosomal 1 tinctoria 1 test 1 target 1 synthesis 1 syn 1 sprout 1 sponge 1 specie 1 seed 1 screening 1 result 1 resistance 1 produce 1 process Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 6320 compound 4469 activity 2786 cell 1740 virus 1674 drug 1606 inhibitor 1559 derivative 1457 % 1425 study 1350 group 1159 acid 1091 effect 1025 structure 1000 basis 975 value 960 inhibition 950 plant 940 synthesis 905 protein 879 h 831 concentration 819 result 795 agent 782 molecule 740 reaction 709 coumarin 700 interaction 695 treatment 694 disease 666 model 661 assay 631 r 622 infection 614 receptor 605 method 605 enzyme 587 ring 582 property 570 type 552 series 549 product 536 cancer 522 target 497 c 491 figure 487 line 483 candidate 482 mouse 475 mechanism 475 b Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 1083 Mannich 879 al 876 Fig 820 . 680 et 640 SARS 524 IC 456 mg 445 Synthesis 398 C 300 N 299 CoV-2 290 A 262 Table 257 CoV 250 CH 245 RNA 235 HIV 234 H 217 P. 209 D 199 mL 195 B 189 II 185 HIV-1 179 USA 172 EC 160 M 158 I. 150 NMR 149 HCV 148 kg 145 ¼ 143 K 142 E. 140 tinctoria 140 L. 133 S. 132 QSAR 131 ± 129 corylifolia 125 University 121 CCR5 121 C. 118 F 115 Figure 114 L 113 IC50 112 R 110 MERS Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 1351 it 888 we 526 they 267 i 220 them 52 itself 47 us 31 bglu 24 themselves 17 one 11 me 9 you 7 he 3 nr-818 2 mrnas 2 he16 2 63a 1 smaller/ 1 ser146 1 s 1 ours 1 o*-orbital 1 nf279 1 indole-2-carboxamides 1 ile235 1 i-[(3'-allyl-2'-hydroxybenzilidene)amino]-3-hydroxyguanidine 1 hdp-(s)-hpmpa 1 chembl1800935 1 bbg100 1 7methylimidazo[1,2-c]pyrimidine 1 30e34 Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 19061 be 3243 have 2250 use 1850 show 812 base 688 compare 685 inhibit 679 find 638 contain 638 bind 636 include 610 obtain 577 evaluate 573 give 534 report 530 test 526 exhibit 524 synthesize 475 produce 464 derive 441 increase 436 induce 415 result 415 follow 406 lead 398 do 397 reduce 392 determine 387 cause 381 know 379 treat 379 suggest 375 identify 374 observe 374 develop 363 isolate 354 perform 344 provide 330 indicate 310 describe 307 involve 306 demonstrate 293 study 292 consider 281 add 275 substitute 273 relate 272 select 257 present 250 calculate Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1604 - 1410 also 1051 not 1029 high 1022 active 1019 anti 979 more 948 new 925 antiviral 892 human 885 other 884 most 808 potent 762 such 743 well 634 different 626 molecular 607 biological 548 novel 544 only 532 low 521 inhibitory 519 viral 497 respectively 466 further 459 potential 453 as 448 good 438 several 434 then 426 natural 422 thus 410 however 383 important 379 many 376 antibacterial 371 effective 370 clinical 363 same 356 significant 345 antifungal 337 similar 328 various 324 inflammatory 319 first 317 less 310 small 296 cytotoxic 294 resistant 291 structural Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 183 most 151 good 120 high 82 least 50 Most 46 low 26 strong 19 great 17 large 10 near 10 late 9 simple 5 old 4 postharv 3 steep 3 short 3 long 3 early 3 W706 2 small 2 hexose 2 fast 2 deep 2 carbonecarbon 2 bad 2 -t 1 wide 1 weak 1 slim 1 safe 1 rich 1 preharv 1 mighty 1 knear 1 innermost 1 fine 1 close 1 broad 1 big 1 Least 1 -d 1 -butenyl)-5-fluoro 1 -NS3-NS4A 1 -DOPA 1 -CL 1 -CHO Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 701 most 52 least 16 well 4 highest 1 long 1 fast Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 1 venkatesanj@bitmesra.ac.in 1 vatalay@metu.edu.tr 1 deposit@ccdc.cam.ac.uk 1 amy.patick@pfizer.com Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 23 compounds were also 12 cells were then 11 activity was also 11 compounds did not 11 mannich base derivatives 10 compounds showed significant 10 compounds were active 8 compound was not 7 compound showed significative 7 compounds are not 7 compounds do not 7 compounds were more 6 cells were pre 6 compound was also 6 compounds were able 6 compounds were further 6 compounds were inactive 6 compounds were then 6 derivatives were more 6 studies are necessary 6 virus induced cpe 5 cells do not 5 cells using mtt 5 compounds were not 5 group did not 5 mannich base moiety 4 acid was also 4 acid were not 4 bases were more 4 compounds are currently 4 compounds are responsible 4 compounds have also 4 compounds showed excellent 4 compounds showed moderate 4 compounds was also 4 coumarin based fluorescent 4 coumarin was completely 4 derivatives have also 4 derivatives showed good 4 plant is also 3 acid is able 3 activity increases too 3 activity using chicoric 3 agent causing chromatin 3 cells were further 3 compound did not 3 compound is able 3 compound is not 3 compound was umbelliprenin 3 compounds are better Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 3 compound was not toxic 2 plant is not able 1 % were not sure 1 . is not as 1 activity is not present 1 activity producing no cure 1 agents are not very 1 agents did not consistently 1 agents has not yet 1 compound has no direct 1 compound is not effective 1 compound showed no clinically 1 compound showed no significant 1 compound showed no toxicity 1 compound was not active 1 compounds are not cytotoxic 1 compounds are not effective 1 compounds are not only 1 compounds are not uniformly 1 compounds are not very 1 compounds are not well 1 compounds had no effect 1 compounds have no importance 1 compounds showed no activity 1 compounds showed no hypoxia 1 compounds were not active 1 compounds were not as 1 compounds were not cytotoxic 1 compounds were not toxic 1 derivative showing no toxicity 1 derivatives are not virucidal 1 drugs find not sufficient 1 drugs is not widespread 1 group has not previously 1 group was not present 1 group was not visible 1 group was not well 1 molecule had no direct 1 plant causing no visible 1 protein has no counterpart 1 result was not significant 1 results were not very 1 study showed no antidepressant 1 study were not suffi 1 synthesis is not problematic A rudimentary bibliography -------------------------- 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 keywords = 3TNT; SARS; compound; study 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. 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 keywords = QSAR; SARS; compound; table 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. 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 keywords = Psoralea; activity; compound; corylifolia; extract; plant; seed 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) . 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 keywords = Candida; IC50; MIC; Pechmann; Synthesis; XII; activity; cell; compound; coumarin; derivative; figure; scheme; study 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. 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 keywords = Fig; SAL; Synthesis; activity; bglu; compound; glucuronidase; inhibitor 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. 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 keywords = QSAR; compound; descriptor; model; screening; virtual 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. 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 keywords = ACE2; SARS; compound 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. 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 keywords = antiviral; compound; disease; test; virus 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. 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 keywords = Fig; HSV-2; cell; compound; virus 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) . 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 keywords = ENPP1; Fig; compound; inhibitor 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) . 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 keywords = SERT; Series; compound; figure 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. 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 keywords = acid; compound; influenza summary = 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 keywords = compound 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 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 keywords = COVID-19; Fig; SARS; TGF; TNF; Thermo; cell; compound 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 ). 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 keywords = Pseudomonas; compound; phenol; wound summary = 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 keywords = activity; compound 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] . 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 keywords = compound; target 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. 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 keywords = compound; food; fruit; product 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). 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 keywords = COVID-19; compound 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. 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 keywords = Plasmodium; chloroquine; compound; figure; resistance summary = 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 keywords = Jurkat; cell; compound; figure summary = 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 keywords = Andrographolide; Kcal; SARS; compound 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 . 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 keywords = activity; compound; drug; isolate; marine; product; sponge 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]. 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 keywords = activity; compound; feline 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. 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 keywords = Boc; compound 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) . 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 keywords = Synthesis; activity; compound summary = 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 keywords = Synthesis; compound; nmr 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 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 keywords = class; compound; metabolic; pathway summary = 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 keywords = Aldrich; Germany; Poland; cell; compound 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). 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 keywords = cell; compound 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. 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 keywords = NBO; compound; figure 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. 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 keywords = PEDV; compound 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 ). 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 keywords = compound 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. 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 keywords = Brassica; ROS; broccoli; compound; effect; sprout; table 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. 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 keywords = COX-2; LMQC50; LMQC72; compound; figure; lmqc36; structure 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. 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 keywords = DEN-2; JEV; compound 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. 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 keywords = Ebola; compound; virus 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. 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 keywords = activity; compound 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. 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 keywords = BVM; HIV-1; SARS; compound; figure 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. 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 keywords = Flu; PB1; compound 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. 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 keywords = CPE; antiviral; compound; effect 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. 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 keywords = CCR5; CXCR4; HIV; compound; figure 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] . 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 keywords = activity; compound 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. doi = 10.1007/s11094-020-02187-x id = cord-264316-do0px1gq author = Mucha, Artur title = Metallo-aminopeptidase inhibitors date = 2010-05-10 keywords = APN; Fig; acid; aminopeptidase; compound; enzyme; inhibitor 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. 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 keywords = DCM; VZV; compound; virus 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 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 keywords = NS2B; compound; dengue; pro summary = 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 keywords = activity; antibiotic; compound; gram; group; scheme 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). 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 keywords = activity; anti; compound; figure; trypanosomal 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. 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 keywords = CoV; Fig; MERS; SARS; compound 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. 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 keywords = Fig; Mannich; Synthesis; activity; basis; candidate; compound; mic 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] . 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 keywords = MCF-7; activity; compound; derivative; gram; scheme 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] . 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 keywords = COV-2; SARS; compound 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. 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 keywords = Botrytis; Fusarium; Muscodor; Penicillium; Rhizoctonia; Streptomyces; activity; antifungal; compound; endophytic; fungus; isolate; pathogen; phytoalexin; plant 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. 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 keywords = compound; curcumin 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. 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 keywords = Isatis; chinese; compound; extract; leave; tinctoria 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 doi = 10.3390/plants9030298 id = cord-016425-8yd2bkf1 author = Strobel, Gary title = Novel Natural Products From Rainforest Endophytes date = 2005 keywords = Pestalotiopsis; Taxus; compound; endophyte; fungus; plant; produce summary = 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 keywords = activity; compound; diarylheptanoid 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. 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 keywords = Table; compound; virus 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 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 keywords = BVDV; HCV; RNA; compound 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. 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 keywords = DHFR; RSV; antiviral; compound; virus 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. 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 keywords = COVID-19; CoV-2; MERS; SARS; cell; compound 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. 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 keywords = Fig; Fluorouracil; Phase; compound; derivative; effect; process; scheme; synthesis 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. 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 keywords = CBS; bismuth; compound summary = 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 keywords = Administration; Drug; FDA; Food; States; compound 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] . 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 keywords = Table; alkaloid; compound; defense; herbivore; number; pas; plant; specie summary = 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 keywords = Lewy; Parkinson; compound; syn summary = 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 keywords = Boc; cell; compound 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). 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 keywords = TSH; compound; hsv-1 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. doi = 10.3390/md11114176 id = cord-020010-q58x6xb0 author = nan title = 19th ICAR Abstracts: date = 2006-03-13 keywords = CDV; Department; HCMV; HCV; HIV; HIV-1; Institute; REP; RNA; Research; ST-246; Sciences; USA; University; Virology; WNV; activity; antiviral; cell; compound; dna; infection; virus 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. 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 keywords = Fig; NMR; chemical; compound; datum; model; molecular; result; structure 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. doi = 10.1002/qsar.19900090309