Synthesis and biological evaluation of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides as antimitotic agents
| Autor: | V. Lakshma Nayak, Mirza Feroz Baig, Ahmed Kamal, Budaganaboyina Prasad, N. V. Subba Reddy, P. S. Srikanth, Korrapati Suresh Babu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Aminopyridines
Apoptosis Antimitotic Agents 01 natural sciences Biochemistry Polymerization HeLa Structure-Activity Relationship Tubulin Annexin Cell Line Tumor Drug Discovery Animals Humans Cytotoxicity Molecular Biology Sheep Domestic Cell Proliferation Membrane Potential Mitochondrial A549 cell Molecular Structure biology 010405 organic chemistry Chemistry Organic Chemistry Active site Triazoles Cell cycle biology.organism_classification Molecular biology Tubulin Modulators Rats 0104 chemical sciences G2 Phase Cell Cycle Checkpoints Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Cell culture Drug Design biology.protein Drug Screening Assays Antitumor Protein Binding |
| Zdroj: | Bioorganic Chemistry. 83:535-548 |
| ISSN: | 0045-2068 |
| Popis: | A library of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides (7a–al) have been designed, synthesized and screened for their anti-proliferative activity against some selected human cancer cell lines namely DU-145, A-549, MCF-7 and HeLa. Most of them have shown promising cytotoxicity against lung cancer cell line (A549), amongst them 7f was found to be the most potent anti-proliferative congener. Furthermore, 7f exhibited comparable tubulin polymerization inhibition (IC50 value 2.04 µM) to the standard E7010 (IC50 value 2.15 µM). Moreover, flow cytometric analysis revealed that this compound induced apoptosis via cell cycle arrest at G2/M phase in A549 cells. Induction of apoptosis was further observed by examining the mitochondrial membrane potential and was also confirmed by Hoechst staining as well as Annexin V-FITC assays. Furthermore, molecular docking studies indicated that compound 7f binds to the colchicine binding site of the β-tubulin. Thus, 7f exhibits anti-proliferative properties by inhibiting the tubulin polymerization through the binding at the colchicine active site and by induction of apoptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect