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

Abstract

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±0.20 μM and 6.92±4.80 μM respectively, compared to Doxorubicin. Additionally, butyl substituted compound 9 m showed superior activity against MDA‐MB‐231 cells with IC₅₀ value of 7.61±5.90 μM. 4‐fluorobenzyl substituted compound 9 c indicated activity on par with the Doxorubicin against MCF‐7 cells with an IC₅₀ value of 9.15±0.10 μM. 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.