Synthesis, biological evaluation and molecular docking studies of novel 1-(4,5-dihydro-1H-pyrazol-1-yl)ethanone-containing 1-methylindol derivatives as potential tubulin assembling inhibitors

摘要：

　　A series of novel compounds(6a-6v)containing 1-methylindol and 31-(4,5-dihydro-1H-pyrazol-1-yl)ethanone skeleton were designed,synthesized and biologically evaluated as potential tubulin polymerization inhibitors and anticancer agents.Among them,compound 6q showed the most potent tubulin polymerization inhibitory activity(IC50 = 1.98 μM)and in vitro growth inhibitory activity against A549,MCF-7 and HepG2 cell lines,with IC50 values of 0.15 μM,0.17 μM,and 0.25 μM respectively,being comparable to the positive control.Furthermore,compound 6q was a potent inducer of apoptosis in A549 cells and it had typical cellular effects for microtubule interacting agents,causing arrest of the cell cycle in G2/M phase.Confocal microscopy assay and molecular docking results further demonstrated that 6q could bind tightly to the colchicine-site of tubulin and act as an anti-tubulin agent.These studies,along with 3D-QSAR modeling provided an important basis for further optimization of compound 6q as a potential anticancer agent.

关键词： tubulin inhibitors 1-methylindol pyrazoline molecular docking

作者: Meng-Ru Yang Ya-Juan Qin Chen Chen Ya-Liang Zhang Bo-Yan Li Tian-Bao Liu Hai-Bin Gong Bao-Zhong Wang Hai-Liang Zhu

作者单位: State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210093,People”s Repu Xuzhou Central Hospital,Xuzhou 221009,People”s Republic of China

会议类型: 国内会议

会议名称: 第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)

会议地点: 太原

会议语种:英文

页码: 480-520

在线出版日期: 2018-05-01（万方平台首次上网日期，不代表论文的发表时间）