Synthesis, biological evaluation and molecular modeling of 1H-benzo[d]imidazole derivatives as novel anti-tubulin polymerization agents†
A series of novel compounds (8a–21b) were designed and synthesized based on 1H-benzo[d]imidazole. Their biological activities were evaluated as potential tubulin polymerization inhibitors and anticancer agents. Among all the compounds, compound 18b showed the most potent in vitro growth inhibitory activity against A549, MCF-7, K562 cancer cell lines, with IC50 values of 0.12 μM, 0.15 μM, 0.21 μM, respectively. And, compound 18b also exhibited significant tubulin polymerization inhibitory activity (IC50 = 2.1 μM), which was comparable with the positive control. Furthermore, docking simulation and 3D-QSAR modeling of inhibitor analogues provide determination of the probable binding model and an important basis that compound 18b with potent inhibitory activity in tumor growth may be a potential anticancer agent.