Yan Tian-Long, Bai Li-Fei, Zhu Hai-Liang, Zhang Wei-Ming, Lv Peng-Cheng
Nanjing Institute for the Comprehensive Utilization of Wild Plants, Nanjing, 210042, P.R. China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210046, P.R. China.
ChemMedChem. 2017 Jul 6;12(13):1087-1096. doi: 10.1002/cmdc.201700271. Epub 2017 Jun 27.
Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell lines (MCF-7, HeLa, HepG2, and A549). In vitro biological evaluations against these human tumor cell lines indicate that most of the prepared compounds have antiproliferative activities; compound 3 a (3β-hydroxy-30-(4-phenyl-1-piperazinyl)olean-12-ene-11,30-dione) exhibited the best inhibitory activity against MCF-7 cells, with an IC value of 1.08 μm. Compound 3 a also showed the most potent inhibitory activity against VEGFR2 tyrosine kinase, with an IC value of 0.35 μm. Docking simulations were performed with the aim of discovering the binding mode of compound 3 a, and the results indicate that 3 a could bind at the VEGFR2 active site.
血管内皮生长因子受体2（VEGFR2）已被证明在肿瘤血管生成的调节中起主要作用。合成了一系列新型甘草次酸衍生物，并评估了它们对VEGFR2的抑制活性以及对四种癌细胞系（MCF-7、HeLa、HepG2和A549）的抗增殖特性。针对这些人类肿瘤细胞系的体外生物学评估表明，大多数制备的化合物具有抗增殖活性；化合物3a（3β-羟基-30-（4-苯基-1-哌嗪基）齐墩果-12-烯-11,30-二酮）对MCF-7细胞表现出最佳抑制活性，IC值为1.08μm。化合物3a对VEGFR2酪氨酸激酶也表现出最有效的抑制活性，IC值为0.35μm。进行对接模拟以发现化合物3a的结合模式，结果表明3a可以结合在VEGFR2活性位点。
