Synthesis, molecular docking and biological evaluation of 1-phenylsulfonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as novel potential tubulin assembling inhibitors.

Research paper by Yan-Ting YT Wang, Xun-Chao XC Cai, Tian-Qi TQ Shi, Ya-Liang YL Zhang, Zhong-Chang ZC Wang, Chang-Hong CH Liu, Hai-Liang HL Zhu

Indexed on: 30 Dec '16Published on: 30 Dec '16Published in: Chemical Biology & Drug Design


A series of new 1-phenylsulfonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC50 = 1.41 μM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF-7 cell lines in vitro with GI50 value of 1.6, 2.7, 2.9 and 4.3 μM, respectively comparable with the positive control colchicine (GI50 value of 4.1, 7.2, 9.5 and 14.5 μM, respectively) and CA-4 (GI50 value of 2.2, 4.3, 6.4 and 11.4 μM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine binding site and act as a tubulin inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future. This article is protected by copyright. All rights reserved.