从 Harrisonia perforata 中分离得到的 16-去甲柠檬苦素是有前景的选择性 11β-HSD1 抑制剂。
16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors.
机构信息
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China.
College of Forestry, Southwest Forestry University/Key Laboratory of Forest Disaster Warning and Control of Yunnan Province, Kunming 650224, P. R. China.
出版信息
Sci Rep. 2016 Nov 11;6:36927. doi: 10.1038/srep36927.
Two new 16-nor limonoids, harperspinoids A and B (1 and 2), with a unique 7/5/5/6/5 ring system, have been isolated from the plant Harrisonia perforate together with a known one, Harperforin G (3). Their structures were elucidated by NMR spectroscopy, X-ray diffraction analysis and computational modelling. Compound 1 exists as polymorphic crystals. Conformations of 1 in solution were further discussed based on the computational results. These compounds exhibited notable inhibitory activity against the 11β-HSD1 enzyme. Compound 3 had potencies for the inhibition of human 11β-HSD1 with high selectivity against 11β-HSD2 (IC 0.58 μM, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism.
从植物哈里斯onia perforate 中分离得到了两种新的 16-去甲柠檬苦素，哈珀斯派诺因 A 和 B（1 和 2），它们具有独特的 7/5/5/6/5 环系统，以及一种已知的化合物 Harperforin G（3）。通过 NMR 光谱、X 射线衍射分析和计算建模阐明了它们的结构。化合物 1 以多晶型晶体的形式存在。根据计算结果进一步讨论了 1 在溶液中的构象。这些化合物对 11β-HSD1 酶表现出显著的抑制活性。化合物 3 对人 11β-HSD1 的抑制作用具有高选择性（IC0.58 μM，SI>174），对 11β-HSD2 具有抑制活性。分子对接和定量构效关系研究揭示了一种混合调节机制。
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