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

Abstract

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 4 showed potent cytotoxicity on Hep-G2 cell lines, while compound 9 showed potent cytotoxicity on the MCF-7 cell line, whereas compounds 10 and 12 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 4, 9, 10, and 12 have potent antiproliferative properties. An in vitro 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.

Graphical Abstract

Keywords:

• Cytotoxicity
• EGFR
• MCF-7
• molecular docking
• quinazolinone

Disclosure statement

No potential conflict of interest was reported by the author(s).