Structure-based design, synthesis and antiproliferative action of new quinazoline-4-one/chalcone hybrids as EGFR inhibitors

• Published in: Journal of molecular structure 2022-04, Vol.1254, p.132422, Article 132422
• Main Authors: Hisham, Mohamed, Hassan, Heba A., Gomaa, Hesham A.M., Youssif, Bahaa G.M., Hayallah, Alaa M., Abdel-Aziz, Mohamed
• Format: Article
• Language: English
• Subjects: Apoptosis; Cancer; Chalcone; NMR; Quinazoline
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132422

•A series of novel quinazoline-4-one/chalcone hybrids as EGFR inhibitors has been designed and synthesized.•Compounds 19, 20, and 22 were the most active antiproliferative agents.•Compounds 19, 20, and 22 display good inhibition of EGFR and elevate caspase-3, 8, and 9 levels.•Compound 19 induced apoptosis and demonstrated cell cycle arrest in both pre-G1 and G2/M phases.•Docking study revealed high binding affinities toward EGFR. A new series of quinazoline-4-one/chalcone hybrids, 7–26, was synthesized in this study as EGFR inhibitors with antiproliferative activity. Target compounds were synthesized and in vitro tested against different cancer cell lines, EGFR, and BRAF enzymes. Three compounds showed the greatest antiproliferative activity and were the most potent EGFR inhibitors. Also, these three compounds improved the level of active caspase-3, 8, and 9 with potent induction of cytochrome c and Bax levels, as well as down regulation of Bcl-2 levels. Finally, the most active inhibitors docked well inside EGFR active sites. [Display omitted]