<i>S</i>-Alkylated quinazolin-4(3<i>H</i>)-ones as dual EGFR/VEGFR-2 kinases inhibitors: design, synthesis, anticancer evaluation and docking study
Samar S. Tawfik, Abdelrahman Hamdi, Ahmed R. Ali, Abdullah A. Elgazar, Hamed W. El-Shafey, Adel S. El‐Azab, Ahmed H. Bakheit, Mohamed Hefnawy, Hazem A. Ghabbour, Alaa A.‐M. Abdel‐Aziz
Abstract
= 5.47-7.26 μM). Dual EGFR/VEGFR-2 inhibitory activities of the most active analogues (4, 11, and 20) were investigated. Compound 4 showed comparable EGFR/VEGFR-2 inhibitory activity to the used control drugs. Flow cytometric analysis indicates that the most potent analogue 4 stopped the cell cycle at the G1 phase and induced 46.53% total apoptosis in HCT-116 cells that was much more powerful than the untreated cells with 2.15% apoptosis. Molecular docking and dynamic simulations of 4, 11, and 20 with EGFR and VEGFR-2 were performed to examine the binding mode and interaction within the enzyme binding pockets.