【摘 要】
：
A series of new 1-phenylsulfonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed,synthesized and evaluated as potential inhibitors of tubulin
【机 构】
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StateKeyLaboratoryofPharmaceuticalBiotechnology,NanjingUniversity,Nanjing210093,P.R.China
【出 处】
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第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)
论文部分内容阅读
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.
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