Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies
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Date
2020
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Abstract
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. © 2020 Elsevier B.V.
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Antineoplastic Agents , Apoptosis , Benzimidazoles , Cell Line, Tumor , Drug Screening Assays, Antitumor , G2 Phase Cell Cycle Checkpoints , Humans , 2 [5,6 dichloro 2 ethyl 1h benzimidazol 1 yl] n'[4 bromophenylene]acetohydrazide , 2 [5,6 dichloro 2 ethyl 1h benzimidazol 1 yl]acetohydrazide , 2 [[5,6 dichloro 2 ethyl 1h benzimidazol 1 yl]acetyl] n phenylhydrazine carbothioamide , 5 [[5,6 dichloro 2 ethyl 1h benzimidazol 1 yl]methyl] 4 phenyl 4h 1,2,4 triazole 3 thiol , antineoplastic agent , benzimidazole derivative , ethyl[5,6 dichloro 2 ethyl 1h benzimidazol 1 yl]acetate , fluorouracil , protein p53 , unclassified drug , antineoplastic agent , benzimidazole derivative , apoptosis , Article , cell cycle , cell cycle progression , cell population , controlled study , drug cytotoxicity , drug structure , drug synthesis , DU145 cell line , G2 phase cell cycle checkpoint , H69AR cell line , HEK293 cell line , human , human cell , IC50 , in vitro study , MCF-7 cell line , MTT assay , apoptosis , drug effect , drug screening , synthesis , tumor cell line