Design, synthesis, biological evaluation, and molecular docking of novel quinazolinone EGFR inhibitors as targeted anticancer agents

A novel series of 2-methyl-3-phenylquinazolin-4-one derivatives were synthesized and biologically evaluated for their cytotoxic potential against MCF-7, HepG2, and PC-3 cancer cells. Most of the tested compounds showed reasonable safety in the normal human skin melanocyte HFB4 cell line. Compound <b>4</b> showed potent cytotoxicity on Hep-G2 cell lines, while compound <b>9</b> showed potent cytotoxicity on the MCF-7 cell line, whereas compounds <b>10</b> and <b>12</b> showed potent cytotoxicity on Hep-G2 cell lines using 5-fluorouracil as a reference standard. Cell division analysis on the tested cell lines revealed that compounds <b>4</b>, <b>9</b>, <b>10</b>, and <b>12</b> have potent antiproliferative properties. An <i>in vitro</i> enzymatic inhibition assay against EGFR-TK confirmed that those compounds have potent EGFR inhibitory activity. The target compounds arrested the cell cycle at the pre-G1 and G2/M phases. Molecular docking simulations showed that all the target compounds possess a common binding pattern like that of Erlotinib.