Design and Synthesis of Various Aryl Amide Derivatives of Imidazo[1,5‐a] Pyridine‐1,2,4‐Thiadiazoles:In‐vitro Cytotoxicity Evaluation and In‐silico

A new series of various aryl amide derivatives of imidazo[1,5‐a]pyridine‐1,2,4‐thiadiazoles (15a‐j) were designed, synthesized and evaluated for their cytotoxic profiles against four human cancer cell lines such as breast cancer (MCF‐7), lung cancer (A549), colon cancer (Colo‐205) and ovarian cancer (A2780) by using of MTT assay with etoposide as standard known chemotherapeutic agent. The five compounds 15a, 15b, 15c, 15f and 15j were exhibited more potent cytotoxic effect compared with etoposide. Among them, compound 15a exhibited potent cytotoxic effect against MCF‐7, A549, Colo‐205, and A2780 cell lines with IC50 values of 0.11±0.045 µM, 0.94±0.047 µM, 0.39±0.023 µM, and 0.77±0.062 µM respectively. Though docking simulations of Human Topoisomerase IIβ, it is apparent that compounds 15a, 15b, 15c, and 15f manifested exceptional binding affinity and interaction profiles, surpassing other compounds evaluated in this in silico study.