Synthesis and biological evaluation of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides as antimitotic agents.

Autor: Prasad B; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India., Lakshma Nayak V; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., Srikanth PS; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., Baig MF; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., Subba Reddy NV; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India., Babu KS; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India., Kamal A; Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, 110 062 New Delhi, India. Electronic address: ahmedkamal@iict.res.in.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Mar; Vol. 83, pp. 535-548. Date of Electronic Publication: 2018 Nov 03.
DOI: 10.1016/j.bioorg.2018.11.002
Abstrakt: 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 (IC 50 value 2.04 µM) to the standard E7010 (IC 50 value 2.15 µM). Moreover, flow cytometric analysis revealed that this compound induced apoptosis via cell cycle arrest at G 2 /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.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: