a Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing , P. R. China.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):124-133. doi: 10.1080/14756366.2018.1533822.
HGF/c-Met signalling pathway plays an important role in the development of cancers. A series of 6,7-dimethoxy-4-anilinoquinolines possessing benzimidazole moiety were synthesised and identified as potent inhibitors of the tyrosine kinase c-Met. Their in vitro biological activities against three cancer cell lines (A549, MCF-7, and MKN-45) were also evaluated. Most of these compounds exhibited moderate to remarkable potency. Among them, compound 12n showed the most potent inhibitory activity against c-Met with IC value of 0.030 ± 0.008 µM and it also showed excellent anticancer activity against the tested cancer cell lines at low micromolar concentration. Molecular docking verified the results and revealed the possible binding mode of the most promising compound 12n into the ATP-binding site of c-Met kinase.
HGF/c-Met 信号通路在癌症的发展中起着重要作用。一系列含有苯并咪唑部分的 6,7-二甲氧基-4-苯胺喹啉被合成并鉴定为酪氨酸激酶 c-Met 的有效抑制剂。它们对三种癌细胞系（A549、MCF-7 和 MKN-45）的体外生物活性也进行了评估。这些化合物大多数具有中等至显著的活性。其中，化合物 12n 对 c-Met 的抑制活性最强，IC 值为 0.030±0.008μM，并且在低微摩尔浓度下对测试的癌细胞系也表现出优异的抗癌活性。分子对接验证了这一结果，并揭示了最有前途的化合物 12n 进入 c-Met 激酶 ATP 结合位点的可能结合模式。
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