Abstract
Purification of the apolar extracts of the marine ascidian Phallusia fumigata, afforded two new sulfated sterols, phallusiasterols A (1) and B (2). The structures of the new compounds have been elucidated using mass spectrometry and NMR experiments. The effects of phallusiasterols A and B as modulators of pregnane-X-receptor (PXR) have been investigated. These studies revealed that phallusiasterol A induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target genes CYP3A4 and MDR1 in the same cell line. Molecular docking calculations suggested the theoretical binding mode of phallusiasterol A with hPXR and revealed that phallusiasterol A fitted well in the LBD of PXR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / genetics
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Animals
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Cholestanol / analogs & derivatives*
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Cholestanol / chemistry
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Cholestanol / isolation & purification
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Cholestanol / pharmacology
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Cytochrome P-450 CYP3A / genetics
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Gene Expression Regulation / drug effects
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Hep G2 Cells
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Humans
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Mediterranean Sea
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Molecular Docking Simulation
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Pregnane X Receptor
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Receptors, Steroid / drug effects*
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Receptors, Steroid / metabolism
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Sterols / chemistry
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Sterols / isolation & purification
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Sterols / pharmacology
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Sulfuric Acid Esters / chemistry
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Sulfuric Acid Esters / isolation & purification
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Sulfuric Acid Esters / pharmacology*
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Urochordata / metabolism*
Substances
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3,6-dihydroxycholestan-5-yl sulfate
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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Pregnane X Receptor
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Receptors, Steroid
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Sterols
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Sulfuric Acid Esters
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Cholestanol
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human