Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp. MK756-CF1.

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.

• Authors: Tatsuro Kawamura, Takahiro Fujimaki, Natsuki Hamanaka, Kentaro Torii, Hiroki Kobayashi, Yoshikazu Takahashi, Masayuki Igarashi, Naoko Kinoshita, Yoshio Nishimura, Etsu Tashiro, Masaya Imoto
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 63 Issue 10 Pg. 601-5 (Oct 2010) ISSN: 1881-1469 [Electronic] England
• PMID: 20736953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Nitro Compounds
• Pyrones
• RNA, Messenger
• SNF 4435C
• arabilin
• spectinabilin
• Prostate-Specific Antigen

Topics

• Androgen Antagonists (chemistry, isolation & purification, pharmacology)
• Binding, Competitive
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Nitro Compounds (isolation & purification)
• Prostate-Specific Antigen (drug effects, genetics)
• Prostatic Neoplasms (drug therapy, pathology)
• Protein Binding
• Pyrones (chemistry, isolation & purification, pharmacology)
• RNA, Messenger (metabolism)
• Spectrum Analysis (methods)
• Stereoisomerism
• Streptomyces (metabolism)