Synthesis and Biological Evaluation of 1-Methyl-1H-indole-Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors
A series of 1-methyl-1H-indole-pyrazoline hybrids were designed,synthesized,and biologically evaluated as potential tubulin polymerization inhibitors.Among them,compound e19 ”5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide” showed the most potent inhibitory effect on tubulin assembly(IC50=2.12 μM)and in vitro growth inhibitory activity against a panel of four human cancer cell lines(IC50 values of 0.21-0.31 μM).Further studies confirmed that compound e19 can induce HeLa cell apoptosis,cause cell-cycle arrest in G2/M phase,and disrupt the cellular microtubule network.These studies,along with molecular docking and 3D-QSAR modeling,provide an important basis for further optimization of compound e19 as a potential anticancer agent.
Ya-Liang Zhang Ya-Juan Qin Dan-Jie Tang Meng-Ru Yang Bo-Yan Li Yan-Ting Wang Yan-Ting Wang Bao-Zhong Wang Hai-Liang Zhu
State Key laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210023(P.R.China) State Key laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210023(P.R.China
国内会议
大连
英文
769-782
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）