Synthesis,biological evaluation and molecular docking studies of novel l-(4,5-dihydro-lH-pyrazol-1-yl)ethanone-containing 1-methylindol derivatives as potential tubulin assembling inhibitors
A series of novel compounds(6a-6v)containing l-methylindol and 31-(4,5-dihydro-lH-pyraxol-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.
tubulin inhibitors 1-methylindol pyrazoline molecular docking
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
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University Nanjing 210093,People”s Repu Xuzhou Central Hospital,Xuzhou 221009,People”s Republic of China
国内会议
大连
英文
834-875
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）