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

ABSTRACT: 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.

SUBMITTER: Yan XH 

PROVIDER: S-EPMC5105127 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature