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Abstract
Cancer represents a group of diseases affecting body tissues causing uncontrolled cell proliferation, tissue invasion and apoptosis. Investigations into cancer therapy have led to the discovery of the active antiangiogenic VEGFR inhibitor vatalanib. This promoted us to design novel phthalazinone derivatives, bearing the same backbone scaffold and having the same pharmacophoric features as vatalanib. Molecular modeling techniques were used to support the design of these compounds as potential antiangiogenic agents by inhibition of vascular endothelial growth factor receptor (VEGFR). The synthesized compounds can be visualized according to the side chain substitution patterns on the phthalazinone core as Mannich base derivatives (IVa-j), substituted benzylidene derivatives (VIIa-g), substituted phenylethylidene derivatives (VIIIa-d), carboxamide derivatives (IXa-d), benzo/3-pyridinylhydrazide derivatives (Xa-c) and substituted pyrazole derivatives (XIa-c). This study covers the synthesis of thirty one novel compounds that were evaluated for their antitumor activity at National Cancer Institute, Cairo University, Egypt, against (MCF-7) breast cancer cell line and (HCT-116) colon cancer cell line. Moreover, the four most active compounds were evaluated for their ability to inhibit (VEGFR) against colon cancer cell line at Vacsera, Egypt