【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
【机 构】
：
StateKeyLaboratoryofPharmaceuticalBiotechnology,NanjingUniversity,Nanjing210093,People'sRepublicofC
【出 处】
：
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 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.
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