Targeting EGFR With Quinazoline-4-One/Chalcone Hybrids: Design, Synthesis, and Anticancer Evaluation

A series of novel quinazoline-4-one/chalcone hybrids (4a-4j) were synthesized and evaluated as epidermal growth factor receptor (EGFR) inhibitors with anticancer activity. The target compounds were in vitro tested against MCF-7 and HepG2 cancer cell lines, and the EGFR enzyme. Compounds 4a and 4g were the most potent EGFR inhibitors (IC_{50  =} 0.09 µM and 0.10 µM, respectively), compared to the standard erlotinib (IC₅₀ = 0.16 µM). Also, they exhibited anticancer activity against both cell lines. They were found to induce cell cycle arrest and apoptosis in MCF-7 and HepG2 cancer cells. Molecular docking revealed that, compounds 4a and 4g bind to the active site of EGFR with the Lys A721 amino acid residue in a manner analogous to Erlotinib. This binding interaction likely contributes to their significant biological activity. Further, dynamic stimulation study that is conducted for compounds 4a and 4g, supports their potency as therapeutic agents in cancer treatment.