Abstract
In the course of screening for a new type of androgen receptor (AR) antagonist, we isolated a novel compound, arabilin, with two structural isomers, spectinabilin and SNF4435C, produced by Streptomyces sp. MK756-CF1. Structure elucidation on the basis of the spectroscopic properties showed that arabilin is a novel polypropionate-derived metabolite with a p-nitrophenyl group and a substituted γ-pyrone ring. Arabilin competitively blocked the binding of androgen to the ligand-binding domain of AR in vitro. In addition, arabilin inhibited androgen-induced prostate-specific antigen mRNA expression in prostate cancer LNCaP cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgen Antagonists / chemistry
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Androgen Antagonists / isolation & purification
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Androgen Antagonists / pharmacology*
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Binding, Competitive
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Male
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Nitro Compounds / isolation & purification
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Prostate-Specific Antigen / drug effects*
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Prostate-Specific Antigen / genetics
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / pathology
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Protein Binding
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Pyrones / chemistry
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Pyrones / isolation & purification
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Pyrones / pharmacology*
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RNA, Messenger / metabolism
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Spectrum Analysis / methods
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Stereoisomerism
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Streptomyces / metabolism*
Substances
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Androgen Antagonists
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Nitro Compounds
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Pyrones
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RNA, Messenger
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SNF 4435C
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arabilin
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spectinabilin
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Prostate-Specific Antigen