Design, Synthesis of Novel Quinazolinone Derivatives and Evaluation of EGFR Kinase Inhibition Activity via In Vitro and In Silico Studies

ABSTRACT

Cancer is one of the most seen diseases worldwide. Due to the serious side effects of anticancer drugs and toxic effects on healthy cells, investigations for novel anticancer agents with low side effects have become one of the most important research areas of our age. With this objective, 17 new compounds were designed and successfully synthesized based on the quinazolinone, which is commonly found in the structures of FDA‐approved EGFR inhibitors, and their structures were elucidated by IR, HRMS, ¹ H, and ¹³ C‐NMR spectral analysis methods. According to cytotoxicity test results, it was determined that compound 4j showed high inhibitory activity compared to cisplatin and gefitinib in the A549 cell line. In apoptosis induction studies, it was observed that compounds 4a , 4b , 4d , and 4f showed activity in the A549 cell line, while compound 4j showed activity in the MCF‐7 cell line. In the study investigating caspase‐3 activation, compounds 4a , 4m , and 4o were found active in the A549 cell line, while compounds 4a and 4o were found active in MCF‐7 cells. In EGFR enzyme inhibition studies, it was observed that the activities of molecules 4b , 4f , and 4j were higher than gefitinib. In silico studies indicated that 4j interacted by establishing significant bonds with both caspase‐3 and EGFR enzyme.