Design, Synthesis, and Cytotoxicity of Some New Benzimidazole‐Piperazine Conjugate Analogues Against Human Breast Adenocarcinoma
Shankaraiah Ambala, Vishnu Thumma, Veerabhadraiah Mallikanti, Shalini Aitha, Raghavender Matta, Jalapathi Pochampally
Abstract
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 IC 50 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 IC 50 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 IC 50 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.