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 μpan class="smallCaps">mpan>) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 values of 0.21–0.31 μpan class="smallCaps">mpan>). 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.
