Polyhydroxylated sterols from the Indonesian soft coral Sinularia sp. and their effect on farnesoid X-activated receptor

Chemical investigation of the Indonesian soft coral Sinularia sp. resulted in the isolation of three known (1, 2 and 7) and five new (3–6 and 8) sterols, characterized by either 24-methylcholestane or gorgostane skeletons. The stereostructures of the new compounds have been elucidated by application of HR-MS and 2D NMR techniques. The isolated steroids have been evaluated for their interaction with the farnesoid X-activated receptor (FXR) and some of them, including the new compound 3 and gorgosterol (7), showed a consistent antagonistic activity, potentially useful for the treatment of cholestasis. The FXR antagonistic activity of gorgosterol (7) was also supported by gene expression experiments. Our results represent the first evaluation of soft coral steroids for interaction with nuclear receptors and qualify gorgosterol (7) as a new chemotype of FXR antagonist.

Gorgosterol is a FXR antagonist.Figure optionsDownload as PowerPoint slideHighlights
► Five new steroids have been isolated from the Indonesian soft coral Sinularia sp.
► Gorgosterol and compound 3 are antagonist of farnesoid X-activated receptor (FXR).
► Structure–activity relationships for FXR antagonism have been drawn.
► Gorgosterol is a new chemotype of FXR antagonist.