Synthesis and biological evaluation of novel indole derivatives containing sulfonamide scaffold as potential tubulin inhibitor
Microtubule-targeted drugs play a critical role in various types of cancer therapy worldwide.In our study,a series of novel indole derivatives containing sulfonamide scaffold were designed,synthesized and biologically evaluated as potential tubulin polymerization inhibitors.Among them,compound 18 displayed the most potent inhibitory effect on antiproliferative activity against four kinds of human cancer cell lines((IC50 values of 0.24-0.59 μM).)and tubulin assembly(IC50 = 1.82 μM).The continued further work demonstrated that compound 18 was a potent inducer of apoptosis in HeLa and could cause cell arrest in the G2/M phase of the cell cycle.Molecular docking and confocal microscopy assay results indicated that compound 18 could bind tightly to the colchicine binding site of tubulin and acted as a tubulin polymerization inhibitor.A 3D-QSAR model was also built to provide more information which could be applied to design new molecules with more potent tubulin inhibitory activity.
Cancer Indole Sulfonamide Tubulin Colchicine Confocal microscopy Molecular docking
Ruo-Jun Man Dan-Jie Tang Xiao-Yuan Lu Yong-Tao Duan Xiang-Xiang Tao Meng-Ru Yang Le-Le Wang Bao-Zhong Wang Chen Xu Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,163 Xianlin Road,Nanjing 210 State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,163 Xianlin Road,Nanjing 210
国内会议
第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)
太原
英文
412-443
2018-05-01（万方平台首次上网日期，不代表论文的发表时间）