6,7-disubstituted-4-anilinoquinazoline: design, synthesis and anticancer activity as a novel series of potent anticancer agents

Epidermal Growth Factor Receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are responsible for several pathological conditions such as the development of different kinds of tumors. The combined inhibition of both signal transduction pathways seems to be a promising novel approach for cancer treatment. In this study, novel 4-anilinoquinazoline derivatives with various substituents on C-7 position of quinazoline moiety were designed, synthesized, and evaluated for their anti-proliferative activity against A431 and HU02 cell lines. Compounds 8a, 8d, and 8f displayed the most potent anticancer activities against A431 (IC50 = 1.78 µM, 8.25 µM, and 7.18 µM, respectively). Molecular docking studies proved that 8a as the most potent compound could be efficiently accommodated in the ATP binding site of EGFR and VEGFR-2 through formation of important hydrogen bonds between quinazoline N1 atom and the Met796 backbone of EGFR as well as the Cys919 backbone of VEGFR-2 with a distance of 1.94 A and 1.398 A, respectively.