Design and Synthesis of Various Aryl Amide Derivatives of Imidazo1,5-a Pyridine-1,2,4-Thiadiazoles: In Vitro Cytotoxicity Evaluation and In Silico Molecular Docking Studies

• Published in: Chemistry & biodiversity 2024-11, p.e202401380
• Main Authors: Ghanta, Srikanth, Chandrasekhar, Choragudi, Sravani, Dasari, Tej, Mandava Bhuvan, Syed, Tasqeeruddin, Kapavarapu, Ravi Kumar, Raju, Rudraraju Ramesh
• Format: Article
• Language: English
• ISSN: 1612-1880; 1612-1880
• DOI: 10.1002/cbdv.202401380

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), via the MTT assay, with etoposide as the standard known chemotherapeutic agent. Five compounds, 15a, 15b, 15c, 15f, and 15j, exhibited more potent cytotoxic effects than did etoposide. Among them, compound 15a exhibited potent cytotoxic effects against the 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. Through docking simulations of human topoisomerase IIβ, it is apparent that compounds 15a, 15b, 15c, and 15f manifested exceptional binding affinities and interaction profiles, surpassing the other compounds evaluated in this in silico study.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), via the MTT assay, with etoposide as the standard known chemotherapeutic agent. Five compounds, 15a, 15b, 15c, 15f, and 15j, exhibited more potent cytotoxic effects than did etoposide. Among them, compound 15a exhibited potent cytotoxic effects against the 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. Through docking simulations of human topoisomerase IIβ, it is apparent that compounds 15a, 15b, 15c, and 15f manifested exceptional binding affinities and interaction profiles, surpassing the other compounds evaluated in this in silico study.