الفهرس 
Synthesis and anticancer activity of some substituted quinazoline derivatives
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Abstract
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The EGFR is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. It is overexpressed, dysregulated or mutated in many epithelial malignancies, and its activation appears important in tumor growth and progression. Many quinazoline derivatives are well acknowledged to possess anticancer and EGFR inhibitory activities e.g.: Gefitinib and Erlotinib. Accordingly, the present study deals with the synthesis of some 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines starting from 4-chloro derivative VI via reaction with either 2-amino-6-(un)substituted benzothiazole, phenolic compounds or hydrazine hydrate to obtain VIIa-c, VIIIa-f, IXa-d or X, respectively. Reaction of the hydrazinyl functionality of X with appropriate acid anhydride, acid chloride or aldehyde affords XIa-c, XIIa-c and XIVa-i, respectively. The target compounds were evaluated for their efficacy as EGFR inhibitors compared to Gefitinib. Candidates eliciting superior EGFR inhibitory activity were further screened for their in vitro cytotoxicity against two human cancer cell lines namely; MCF-7 (breast) and A549 (lung), in addition to normal fibroblast cell (WI38) relative to Gefitinib. The most active compound VIIa was subjected to cell cycle analysis and apoptotic assay. Moreover, a molecular modeling study was performed to figure out the interaction of some selected new compounds with the active site of EGFR-TK and predict their physicochemical, ADME and pharmacokinetic properties