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

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. (C) 2022 Elsevier By. All rights reserved.

Automated summary

A new series of quinazoline-4-one/chalcone hybrids, 7-26, were synthesized and tested as EGFR inhibitors with antiproliferative activity. Three compounds showed the greatest antiproliferative activity and were the most potent EGFR inhibitors. These three compounds improved the levels of active caspase-3, 8, and 9, induced cytochrome c and Bax levels, and down regulated Bcl_2 levels. The most active inhibitors docked well inside EGFR active sites.