Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides

2015 ◽  
Vol 0 (0) ◽  
Author(s):  
Jan Zitko ◽  
Barbora Servusová-Vaňásková ◽  
Pavla Paterová ◽  
Lucie Navrátilová ◽  
František Trejtnar ◽  
...  
Keyword(s):  
Biological Activities ◽  
Inhibiting Activity ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Pyrazinoic Acid

AbstractN-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH

scholarly journals Hybrid cis-stilbene Molecules: Novel Anticancer Agents

2019 ◽  
Vol 20 (6) ◽  
pp. 1300 ◽  
Author(s):  
Natalia Piekuś-Słomka ◽  
Renata Mikstacka ◽  
Joanna Ronowicz ◽  
Stanisław Sobiak
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Distinct Group ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Structure Activity ◽  
Polymerization Inhibitor ◽  
Hybrid Molecules ◽  
Tubulin Polymerization Inhibitor ◽  
Pharmacologically Active

The growing interest in anticancer hybrids in the last few years has resulted in a great number of reports on hybrid design, synthesis and bioevaluation. Many novel multi-target-directed drug candidates were synthesized, and their biological activities were evaluated. For the design of anticancer hybrid compounds, the molecules of stilbenes, aromatic quinones, and heterocycles (benzimidazole, imidazole, pyrimidine, pyridine, pyrazole, quinoline, quinazoline) were applied. A distinct group of hybrids comprises the molecules built with natural compounds: Resveratrol, curcumin, coumarin, and oleanolic acid. In this review, we present the studies on bioactive hybrid molecules of a well-known tubulin polymerization inhibitor, combretastatin A-4 and its analogs with other pharmacologically active entities. The mechanism of anticancer activity of selected hybrids is discussed considering the structure-activity relationship.

scholarly journals Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3327
Author(s):  
Ziad Omran ◽  
Chris P. Guise ◽  
Linwei Chen ◽  
Cyril Rauch ◽  
Ashraf N. Abdalla ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Multidrug Resistant ◽  
Biological Evaluation ◽  
High Chemical ◽  
Design Synthesis ◽  
Hypoxic Conditions ◽  
Cancerous Cell

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

1,5-Benzodiazepine derivatives as potential antimicrobial agents: design, synthesis, biological evaluation, and structure–activity relationships

2015 ◽  
Vol 13 (19) ◽  
pp. 5497-5509 ◽  
Author(s):  
Lan-Zhi Wang ◽  
Xiao-Qing Li ◽  
Ying-Shuang An
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Benzodiazepine Derivatives

36 novel 1,5-benzodiazepine derivatives were synthesized and evaluated for their in vitro antimicrobial activity. The results revealed that most of the 1,5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains.

scholarly journals Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitation

2018 ◽  
Vol 1 (1) ◽  
pp. e00004 ◽  
Author(s):  
D.A. Filimonov ◽  
D.S. Druzhilovskiy ◽  
A.A. Lagunin ◽  
T.A. Gloriozova ◽  
A.V. Rudik ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Expression Profiles ◽  
Molecular Transport ◽  
Chemical Compounds ◽  
Training Set ◽  
Structure Activity Relationships ◽  
Web Resource ◽  
Structure Activity ◽  
Computer Aided

An essential characteristic of chemical compounds is their biological activity since its presence can become the basis for the use of the substance for therapeutic purposes, or, on the contrary, limit the possibilities of its practical application due to the manifestation of side action and toxic effects. Computer assessment of the biological activity spectra makes it possible to determine the most promising directions for the study of the pharmacological action of particular substances, and to filter out potentially dangerous molecules at the early stages of research. For more than 25 years, we have been developing and improving the computer program PASS (Prediction of Activity Spectra for Substances), designed to predict the biological activity spectrum of substance based on the structural formula of its molecules. The prediction is carried out by the analysis of structure-activity relationships for the training set, which currently contains information on structures and known biological activities for more than one million molecules. The structure of the organic compound is represented in PASS using Multilevel Neighborhoods of Atoms descriptors; the activity prediction for new compounds is performed by the naive Bayes classifier and the structure-activity relationships determined by the analysis of the training set. We have created and improved both local versions of the PASS program and freely available web resources based on PASS (http://www.way2drug.com). They predict several thousand biological activities (pharmacological effects, molecular mechanisms of action, specific toxicity and adverse effects, interaction with the unwanted targets, metabolism and action on molecular transport), cytotoxicity for tumor and non-tumor cell lines, carcinogenicity, induced changes of gene expression profiles, metabolic sites of the major enzymes of the first and second phases of xenobiotics biotransformation, and belonging to substrates and/or metabolites of metabolic enzymes. The web resource Way2Drug is used by over 18,000 researchers from more than 90 countries around the world, which allowed them to obtain over 600,000 predictions and publish about 500 papers describing the obtained results. The analysis of the published works shows that in some cases the interpretation of the prediction results presented by the authors of these publications requires an adjustment. In this work, we provide the theoretical basis and consider, on particular examples, the opportunities and limitations of computer-aided prediction of biological activity spectra.

scholarly journals Structure–Activity Relationships and Biological Evaluation of 7-Substituted Harmine Analogs for Human β-Cell Proliferation

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1983 ◽  
Author(s):  
Kunal Kumar ◽  
Peng Wang ◽  
Ethan A. Swartz ◽  
Susmita Khamrui ◽  
Cody Secor ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Activity ◽  
Biological Evaluation ◽  
Activity Relationship ◽  
Β Cell ◽  
Structure Activity Relationships ◽  
Specific Targeting ◽  
Structure Activity

Recently, we have shown that harmine induces β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. We explore structure–activity relationships of the 7-position of harmine for both DYRK1A kinase inhibition and β-cell proliferation based on our related previous structure–activity relationship studies of harmine in the context of diabetes and β-cell specific targeting strategies. 33 harmine analogs of the 7-position substituent were synthesized and evaluated for biological activity. Two novel inhibitors were identified which showed DYRK1A inhibition and human β-cell proliferation capability. The DYRK1A inhibitor, compound 1-2b, induced β-cell proliferation half that of harmine at three times higher concentration. From these studies we can draw the inference that 7-position modification is limited for further harmine optimization focused on β-cell proliferation and cell-specific targeting approach for diabetes therapeutics.

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