16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors.
16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors.
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来自 Harrisonia perforata 的 16-nor 柠檬苦素作为有前景的选择性 11 beta-HSD1 抑制剂
DOI：
10.1038/srep36927
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发表时间：
2016-11-11
影响因子：
4.6
通讯作者：
Hao XJ
中科院分区：
文献类型：
--
作者：
Yan XH;Yi P;Cao P;Yang SY;Fang X;Zhang Y;Bin Wu;Leng Y;Di YT;Lv Y;Hao XJ
两个新的16-Nor柠檬苦素类化合物，HarperspinoidA和B(1和2)，具有独特的7/5/5/6/5环系，与一个已知的Harperperin G(3)一起从穿孔哈里森属植物中分离得到。其结构经核磁共振波谱、X-射线衍射分析和计算模型确证。化合物1以多晶型晶体形式存在。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酶具有显著的抑制活性。化合物3对人11β-HSD1有较强的抑制作用，对11β-HSD2有较高的选择性(IC500.58 μM，SI >； 174)。分子对接和定量构效关系研究揭示了一种混合调控机制。
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 (IC50 0.58 μM, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism.
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影响因子：
5.1
作者：
Khuong-Huu, Q;Chiaroni, A;Khuong-Huu, F
通讯作者：
Khuong-Huu, F
影响因子：
5.1
作者：
Rajab, MS;Rugutt, JK;Fischer, NH
通讯作者：
Fischer, NH
影响因子：
7.3
作者：
Scott, James S.;Goldberg, Frederick W.;Turnbull, Andrew V.
通讯作者：
Turnbull, Andrew V.
影响因子：
4.6
作者：
Sun W;Chen X;Tong Q;Zhu H;He Y;Lei L;Xue Y;Yao G;Luo Z;Wang J;Li H;Zhang Y
通讯作者：
Zhang Y
影响因子：
6.1
作者：
Flack, HD;Bernardinelli, G
通讯作者：
Bernardinelli, G