Design, Synthesis, and Cytotoxicity of Some New Benzimidazole-Piperazine Conjugate Analogues Against Human Breast Adenocarcinoma

New benzimidazole-based piperazine analogues (9 a-n) were synthesized and screened for their cytotoxicity against human breast cancer cell lines MCF-7 and MDA-MB-231 by employing Doxorubicin as a standard reference. 4-(trifluoromethyl)benzyl substituted compound 9 f displayed outstanding activity against both MCF-7 and MDA-MB-231 cell line with IC50 value of 7.29 & PLUSMN;0.20 & mu;M and 6.92 & PLUSMN;4.80 & mu;M respectively, compared to Doxorubicin. Additionally, butyl substituted compound 9 m showed superior activity against MDA-MB-231 cells with IC50 value of 7.61 & PLUSMN;5.90 & mu;M. 4-fluorobenzyl substituted compound 9 c indicated activity on par with the Doxorubicin against MCF-7 cells with an IC50 value of 9.15 & PLUSMN;0.10 & mu;M. The morphological study of active compounds revealed their activity and have not shown any toxicity on MCF-10A cells. Molecular docking study of all compounds against Cyclin-dependent kinase 6 produced notable binding energies and interactions in comparison to co-crystalized ligand Abemaciclib. Pharmacokinetic evaluation of compounds presented favourable drug-likeness properties.

Automated summary

New benzimidazole-based piperazine analogues (9 a-n) were synthesized and screened for their cytotoxicity against human breast cancer cell lines MCF-7 and MDA-MB-231. Compound 9 f showed outstanding activity against both cell lines, and compound 9 m exhibited superior activity against MDA-MB-231 cells. Compound 9 c showed activity on par with Doxorubicin against MCF-7 cells. The active compounds did not show any toxicity on MCF-10A cells and exhibited notable binding energies and interactions with Cyclin-dependent kinase 6.