The aim of the study was to synthesize a new series of benzimidazole derivatives and to investigate the underlying molecular mechanisms of the potential cell cycle inhibition and apoptotic effects against a panel of selected human cancer cell lines along with HEK-293 human embryonic kidney cells. MTT assay was used to evaluate cytotoxic effects. Muse™ Cell Analyzer was used to assess cell cycle progression. Annexin-V/PI staining assay was used for detecting apoptosis. All the synthesized compounds showed a significant cytotoxic effect against cancer cells with the IC₅₀ values between 9.2 and 166.1 μg/mL. Among the tested derivatives, compound 5 showed significant cytotoxic activity against MCF-7, DU-145 and H69AR cancer cells with the IC₅₀ values of 17.8 ± 0.24, 10.2 ± 1.4 and 49.9 ± 0.22 μg/mL respectively. The compounds 5 was also tested on HEK-293 human embryonic kidney cells and found to be safer with lesser cytotoxicity. The results revealed that compound 5 significantly increased cell population in the G₂/M-phase which is modulated by a p53 independent mechanism. Compound 5 caused an increase in the percentage of late apoptotic cells in all tested cancer cells in a concentration-dependent manner. Among all synthesized derivatives, compound 5 the bromo-derivative, showed the highest cytotoxic potential, induced G2/M cell cycle arrest and apoptotic cell death in genotypically different human cancer cells. These results suggest that compound 5 might be a promising agent for cancer therapy and further structural modifications of benzimidazole derivatives may create promising anticancer agents.

这项研究的目的是合成一系列新的苯并咪唑衍生物，并研究潜在的细胞周期抑制和针对一系列选定的人类癌细胞系以及HEK-293人类胚胎肾细胞的凋亡效应的潜在分子机制。使用MTT测定法评估细胞毒性作用。Muse™细胞分析仪用于评估细胞周期进程。Annexin-V / PI染色法用于检测细胞凋亡。所有合成的化合物均显示出对癌细胞的显着细胞毒性作用，IC ₅₀值为9.2至166.1μg/ mL。在测试的衍生物中，化合物5对具有IC _50的MCF-7，DU-145和H69AR癌细胞具有明显的细胞毒性活性分别为17.8±0.24、10.2±1.4和49.9±0.22μg/ mL。还对HEK-293人胚胎肾细胞进行了化合物5的测试，发现更安全，细胞毒性更小。结果表明，化合物5显着增加了G ₂中的细胞数量/ M相是由p53独立机制调制的。在所有测试的癌细胞中，化合物5以浓度依赖性方式引起晚期凋亡细胞百分比的增加。在所有合成的衍生物中，溴衍生物的化合物5在基因型不同的人类癌细胞中显示出最高的细胞毒性潜力，诱导的G2 / M细胞周期阻滞和凋亡性细胞死亡。这些结果表明，化合物5可能是用于癌症治疗的有希望的试剂，并且苯并咪唑衍生物的进一步结构修饰可以产生有希望的抗癌剂。