Equol, a natural estrogenic metabolite from soy isoflavones: Convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta

Rajeev S. Muthyala, Young H. Ju, Shubin Sheng, Lee D. Williams, Daniel R. Doerge, Benita S. Katzenellenbogen, William G. Helferich, John A. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Equol is a metabolite produced in vivo from the soy phytoestrogen daidzein by the action of gut microflora. It is known to be estrogenic, so human exposure to equol could have significant biological effects. Equol is a chiral molecule that can exist as the enantiomers R-equol and S-equol. To study the biological activity of racemic (±)-equol, as well as that of its pure enantiomers, we developed an efficient and convenient method to prepare (±)-equol from available isoflavanoid precursors. Furthermore, we optimized a method to separate the enantiomers of equol by chiral HPLC, and we studied for the first time, the activities of the enantiomers on the two estrogen receptors, ERα and ERβ. In binding assays, S-equol has a high binding affinity, preferential for ERβ (Ki[ERβ]=16 nM; β/α=13 fold), that is comparable to that of genistein (K i[ERβ]=6.7 nM; β/α=16), whereas R-equol binds more weakly and with a preference for ERα (Ki[ERα]=50 nM; β/α=0.29). All equol isomers have higher affinity for both ERs than does the biosynthetic precursor daidzein. The availability and the in vitro characterization of the equol enantiomers should enable their biological effects to be studied in detail.

Original languageEnglish (US)
Pages (from-to)1559-1567
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number6
DOIs
StatePublished - Mar 15 2004

Keywords

  • ER
  • Estrogen Receptor
  • HEC-1
  • HPLC
  • High Performance Liquid Chromatography
  • Human Endometrial Carcinoma Cells-1
  • RBA
  • Relative Binding Affinity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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