Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Arch Pharm (Weinheim). 2016 Aug;349(8):651-61. doi: 10.1002/ardp.201600003. Epub 2016 Jun 10.
A series of novel 4-phenoxyquinoline derivatives containing the benzo[d]thiazole-2-yl urea moiety were synthesized and evaluated for their cytotoxicity against the HT-29, MKN-45, and H460 cell lines. The structures of the target compounds were confirmed by (1) H NMR and MS spectra. Most of them showed moderate to excellent potency against the three tested cell lines. Especially, compound 23 was identified a promising agent (c-Met IC50 = 17.6 nM), showing the most potent anticancer activities with IC50 values of 0.18, 0.06, and 0.01 µM against the HT-29, MKN-45, and H460 cell lines, respectively. The docking results of 23 with the c-Met kinase model 3LQ8 showed a specific binding mode between the ligand and the target protein.
一系列新型 4-苯氧基喹啉衍生物含有苯并[d]噻唑-2-基脲部分，它们的细胞毒性被评估对 HT-29、MKN-45 和 H460 细胞系的影响。目标化合物的结构通过 1 H NMR 和 MS 光谱确认。它们大多数对三种测试的细胞系都表现出中等至优异的效力。特别是，化合物 23 被鉴定为一种有前途的药物（c-Met IC50 = 17.6 nM），显示出最有效的抗癌活性，对 HT-29、MKN-45 和 H460 细胞系的 IC50 值分别为 0.18、0.06 和 0.01 μM。23 与 c-Met 激酶模型 3LQ8 的对接结果显示配体与靶蛋白之间的特定结合模式。
