Synthesis and Biological Evaluation of 1-Methyl-1H-indole-Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors

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• 作者：Ya-Liang Zhang ; Ya-Juan Qin ; Dan-Jie Tang ; Meng-Ru Yang ; Bo-Yan Li ; Yan-Ting Wang ; Hong-Yu Cai ; Prof. Bao-Zhong Wang and Prof. Dr. Hai-Liang Zhu
• 刊名：ChemMedChem
• 出版年：2016
• 出版时间：July 5, 2016
• 年：2016
• 卷：11
• 期：13
• 页码：1446-1458
• 全文大小：2747K
• ISSN：1860-7187

文摘

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.