Synthesis and Biological Evaluation of 1‐Methyl‐1H‐indole–Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors |
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| Authors: | 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 Prof. Dr. Hai‐Liang Zhu |
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| Affiliation: | State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, P.R. China |
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| Abstract: | 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. |
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| Keywords: | apoptosis indole– pyrazolines inhibitors molecular docking tubulin |
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