title: Synthesis and cytotoxic activity of 2-anilinopyridine-3-acrylamides as tubulin polymerization inhibitors.
abstract: In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl-linked acrylamide conjugates were designed, synthesized, and evaluated for cytotoxic activity against various human cancer cell lines, anti-tubulin activity and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6-fluorobenzo[d]thiazol-2-yl)-3-(2-((3,4,5-trimethoxyphenyl)amino)pyridin-3-yl)acrylamide] and 6 p [(E)-3-(2-((4-methoxyphenyl)amino)pyridin-3-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acrylamide] showed promising cytotoxicity, specifically against the A549 human lung adenocarcinoma epithelial cell line, with GI50 values of 0.6±0.23 and 1.8±0.22 μM, respectively. Furthermore, cell-cycle perturbation studies by flow cytometry analysis indicated drastic cell-cycle effects in the G2 /M phase in this cell line followed by caspase-3 activation and apoptotic cell death. Molecular docking studies of the most potent compound, 6 d, revealed that this compound interacts with and binds efficiently in the active site of tubulin.
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007 (India); Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India). ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: Md
authors.initials: M
authors.lastname: Ashraf
authors.forename: M Naseer Ahmed
authors.initials: MN
authors.lastname: Khan
authors.forename: Vijaykumar D
authors.initials: VD
authors.lastname: Nimbarte
authors.forename: Shaikh
authors.initials: S
authors.lastname: Faazil
authors.forename: N V
authors.initials: NV
authors.lastname: Subba Reddy
authors.forename: Shaik
authors.initials: S
authors.lastname: Taj
keywords: 2-anilinopyridine-3-acrylamides; apoptosis; growth inhibition; molecular docking; tubulin polymerization