Synthesis of quinazolinone derivatives and investigation of their anticancer activities

Cancer is one of the most common diseases in humans. Due to the serious side effects of anticancer drugs and their toxic effects on healthy cells, the development of new anticancer agents with low side effects and high selectivity against cancer cells has become one of the most important research areas of our age. For this purpose, seventeen new compounds were designed and synthesized based on the quinazolinone ring structure, which is commonly found in the structures of FDA-approved EGFR inhibitor compounds, and their structures were elucidated by IR, 1H-NMR and 13C-NMR spectral analysis methods. As a result of cytotoxicity tests, it was determined that compound 4j showed high inhibitory activity compared to reference drugs (gefitinib, cisplatin) in the A549 cell line. In apoptosis induction studies, it was observed that compound 4a, 4b, 4d, 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 the MCF-7 cell line. In EGFR enzyme inhibition studies, it was observed that the activities of compounds 4b, 4f and 4j were higher than the standard drug gefitinib. In molecular docking and molecular modeling studies, it was reported that 4j interacted by establishing significant bonds with both caspase-3 and EGFR enzyme.