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: Masteria Yunovilsa Putra, Giorgio Bavestrello, Carlo Cerrano, Barbara Renga, Claudio D'Amore, Stefano Fiorucci, Ernesto Fattorusso, Orazio Taglialatela-Scafati
• Journal: Steroids (Steroids) Vol. 77 Issue 5 Pg. 433-40 (Apr 2012) ISSN: 1878-5867 [Electronic] United States
• PMID: 22252013 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• ABCB11 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters
• Membrane Transport Proteins
• Receptors, Cytoplasmic and Nuclear
• Sterols
• organic solute transporter alpha, human
• farnesoid X-activated receptor
• gorgosterol
• Cholesterol

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Anthozoa (chemistry)
• Cells, Cultured
• Cholesterol (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Gene Expression (drug effects)
• Hep G2 Cells
• Humans
• Hydroxylation
• Indonesia
• Membrane Transport Proteins (genetics, metabolism)
• Molecular Structure
• Primary Cell Culture
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Stereoisomerism
• Sterols (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship
• Transfection