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.
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。
