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- W3169201908 abstract "Epidermal Growth Factor Receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) as appropriate targets for cancer therapy have recently made noteworthy field since the introduction of vadetanib as a dual inhibitor of VEGFR and EGFR tyrosine kinases (TKIs). In this study, twelve quinazoline derivatives were designed, synthesized, and evaluated for their cytotoxicity on A431 (human carcinoma cell) as well as HU02 (Foreskin fibroblast) cell lines by MTT assay. The binding mode of the most potent compound (8a) with EGFR and VEGFR2 was studied using molecular docking. Most of the compounds showed significant inhibition on the growth of A431 cells at the concentration lower than 100 µM. The compound 8a bearing diethylamine along with 4-bromo-2-fluoroaniline exhibited the best cytotoxic activity (IC50=2.62 μM) compared to erlotinib and vandetanib as positive controls. Synthesized compounds did not indicate significant cyttoxicity against HU02 cell line Quinazoline N1 of 8a depicted the shorter hydrogen bonding distance with the residue Met-769 of EGFR (1.719 A) and Cys-919 of VEGFR (2.809 A) in comparison with vandetanib which was consistent with higher cytotoxicity of this compound. Higher potency of 8a may be put down to the flexibility of diethylamine and its higher lipophilicity as well as lower steric hindrance of this substituent." @default.
- W3169201908 created "2021-06-22" @default.
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- W3169201908 date "2020-11-18" @default.
- W3169201908 modified "2023-09-25" @default.
- W3169201908 title "Design, synthesis, biological evaluation and docking study of novel 4-anilinoquinazolines derivatives as anticancer agents" @default.
- W3169201908 doi "https://doi.org/10.30492/ijcce.2020.132389.4271" @default.
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