Synthesis, biological evaluation and molecular docking of thiazole hydrazone derivatives grafted with indole as novel tubulin polymerization inhibitors

Abstract

Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-six novel thiazole hydrazone derivatives grafted with indole were synthesized and estimated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound D11 showed the most excellent inhibition against tubulin assembly (IC50 = 1.68 μM) and in vitro growth inhibitory activity against three human cancer cell lines (IC50 = 0.46, 0.21 and 0.32 μM, respectively for MCF-7, A549 and Hela). Moreover, it can effectively induce apoptosis, block cell cycle in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound D11 as a potential anticancer agent.