Yang Yu-Shun, Su Mi-Mi, Zhang Xu-Ping, Liu Qi-Xing, He Zhen-Xiang, Xu Chen, Zhu Hai-Liang
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China.
Bioorg Med Chem Lett. 2018 Oct 15;28(19):3182-3186. doi: 10.1016/j.bmcl.2018.08.025. Epub 2018 Aug 25.
By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC = 17.2 μM) and Metronidazole (MIC = 31.3 μM). With low cytotoxicity, it showed considerable potential for further development. Docking simulation revealed the possible binding pattern of this series. 3D QSAR model was built to discuss SAR and give useful hints for future modification.
通过从紫草素中提取重要部分，合成了一系列新型的氧代吲哚啉衍生物S1 - S20以抑制幽门螺杆菌脲酶。最有效的化合物S18表现出比阳性对照物AHA（IC = 17.2 μM）和甲硝唑（MIC = 31.3 μM）更好的活性（IC = 0.71 μM；MIC = 0.48 μM）。由于细胞毒性低，它显示出相当大的进一步开发潜力。对接模拟揭示了该系列的可能结合模式。构建了3D QSAR模型以讨论构效关系并为未来的修饰提供有用的提示。
