Designing, Synthesis, and Anti-Breast Cancer Activity of a Series of New Quinazolin-4(1H)-one Derivatives

The inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein could be a promising treatment for breast cancer. In this regard, docking studies were accomplished on various functionalized organic molecules. Among them, several derivatives of quinazolin-4(1H)-one exhibited anti-breast cancer activity and satisfied the drug likeliness properties. Further, the in vitro inhibitory studies by a series of 2-(2-phenoxyquinolin-3-yl)-2,3-dihydroquinazolin-4(1H)-one molecules showed strong anti-cancer activity than the currently available drug, wortmannin. The MTT cytotoxicity assay was used to predict the anti-proliferative activity of these drugs against MCF-7 cancer cells by inhibiting the PIK3CA protein. The dose-dependent analysis showed a striking decrease in cancer cell viability at 24 h with inhibitory concentrations (IC₅₀ ) of 3b, 3c, 3d, 3f and 3m are 15±1, 17±1, 8±1, 10±1 and 60±1 (nanomoles), respectively. This is the first report in the literature on the inhibition of PIK3CA protein by quinazolinone derivatives that can be used in the treatment of cancer. Quinazolinone analogs have the potential to be safe and economically feasible scaffolds if they are produced using a chemical technique that is both straightforward and amenable to modification. From the cancer research perspective, this study can eventually offer better care for cancer patients.