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

J Antibiot (Tokyo). 2010 Oct;63(10):601-5. doi: 10.1038/ja.2010.98. Epub 2010 Aug 25.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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