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Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane x receptor modulation.

DRS at CSIR-National Institute of Oceanography

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Title Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane x receptor modulation.
 
Creator Sepe, V.
DiLeva, F.S.
D'Amore, C.
Festa, C.
DeMarino, S.
Renga, B.
D’Auria, M.V.
Novellino, E.
Limongelli, V.
DeSouza, L.
Majik, M.
Zampella, A.
Fiorucci, S.
 
Subject soft coral
docking simulations
 
Description In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3?-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design.
 
Date 2014-06-11T11:31:16Z
2014-06-11T11:31:16Z
2014
 
Type Journal Article
 
Identifier Marine Drugs , vol.12; 2014; 3091-3115.
http://drs.nio.org/drs/handle/2264/4548
 
Language en
 
Rights © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)
 
Publisher MDPI Publishing