16-nor Limonoids from Harrisonia perforata as promising selective 11β-HSD1 inhibitors

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 mod...

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Detalles Bibliográficos
Autores principales: Yan, Xiao-Hui, Yi, Ping, Cao, Pei, Yang, Shi-Ying, Fang, Xin, Zhang, Yu, Bin Wu, Leng, Ying, Di, Ying-Tong, Lv, Yang, Hao, Xiao-Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105127/
https://www.ncbi.nlm.nih.gov/pubmed/27833136
http://dx.doi.org/10.1038/srep36927
Descripción
Sumario: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(50) 0.58 μM, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism.

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