Discovery and Evaluation of Oxazole-Pyrimidine-Isoquinoline Amides as Anticancer Leads

A series of oxazole-pyrimidine-isoquinoline amides 11a-j is prepared, and their chemical structures were characterized by analogy and spectral data (¹H-NMR, ¹³C-NMR, and mass spectrometry). Further, all analogues were assessed against four human cancer cell lines, such as human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Colo-205), and human ovarian cancer (A2780) by employing the MTT method. The results found that maximum compounds exhibited good to judicious anticancer activities. Those results were compared with the known chemotherapeutic agent Etoposide. Among all, four compounds 11a, 11b, 11c, and 11d displayed remarkable activity than Etoposide. All compounds showed selective cytotoxicity against cancer cells but not against normal Vero cells (IC₅₀ = >24 µM), justifying the designing approach to develop a selective anticancer agent. Subsequently, compound 11a was scrutinized using molecular docking experiments, which evaluate the binding interaction of 11a with topoisomerase enzyme (RSCBPDB: 4gfh) and demonstrated the highest anti-cancer activity than Etoposide.