N -Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-CarboxAmides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents

Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of -phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR ( H and C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds (37.4, 8.9 µM), (50.9, 3.3 µM), (17.0, 5.3 µM), and (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues.