State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, People's Republic of China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, People's Republic of China; Guangxi Biological Polysaccharide Separation, Purification and Modification Research Platform, Guangxi University for Nationalities, Nanning 530006, People's Republic of China.
Bioorg Chem. 2019 Nov;92:103219. doi: 10.1016/j.bioorg.2019.103219. Epub 2019 Aug 26.
Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI = 0.71-2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.
设计、合成并评价了 24 种 1,2-二芳基苯并咪唑衍生物。结果表明，它们大多数都是有潜力的抗癌药物。其中，化合物 c24 表现出最高的抗肿瘤活性（对 HeLa、HepG2、A549 和 MCF-7 细胞的 GI = 0.71-2.41 μM），对正常细胞的毒性较低（对 L02 细胞的 CC > 100 μM）。在微管结合实验中，c24 对微管聚合的抑制作用最强（IC = 8.47 μM）。通过分子对接模拟实验验证了化合物 c24 与微管蛋白晶体的结合能力。进一步对 HepG2 和 HeLa 细胞的研究表明，化合物 c24 可使肿瘤细胞有丝分裂停滞在 G2/M 期，然后诱导细胞凋亡。总之，化合物 c24 是一种很有前途的微管组装抑制剂。
