Discovery of novel 4-anilinoquinazoline derivatives as potent inhibitors of epidermal growth factor receptor with antitumor activity |
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Authors: | Yun-Yun Xu Si-Ning Li Gao-Jian Yu Qing-Hua Hu Huan-Qiu Li |
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Affiliation: | 1. College of Pharmaceutical Science, Soochow University, Suzhou 215123, PR China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China |
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Abstract: | Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR–TK inhibitory activity. Especially, N6-((5-bromothiophen-2-yl)methyl)-N4-(3-chlorophenyl)quinazoline-4,6-diamine (5e), showed the most potent inhibitory activity (IC50 = 3.11 μM for Hep G2, IC50 = 0.82 μM for A549). The EGFR molecular docking model suggested that the new compound is nicely bound to the region of EGFR, and cell morphology by Hoechst stain experiment suggested that these compounds efficiently induced apoptosis of A549 cells. |
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Keywords: | EGFR–TK inhibitors 4-Anilinoquinazoline Antitumor Molecular docking |
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