title: Polyhydroxylated sterols from the Indonesian soft coral Sinularia sp. and their effect on farnesoid X-activated receptor.
abstract: 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.
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Masteria Yunovilsa
authors.initials: MY
authors.lastname: Putra
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bavestrello
authors.forename: Carlo
authors.initials: C
authors.lastname: Cerrano
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fattorusso
authors.forename: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006900:Hydroxylation; D007214:Indonesia; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D061251:Primary Cell Culture; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D013261:Sterols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014162:Transfection; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D026901:Membrane Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013261:Sterols; D000099150:Receptor, Farnesoid X-Activated; C093491:ABCB11 protein, human; C476575:organic solute transporter alpha, human; C021689:gorgosterol