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

Fingerprint

Equol
Estrogen Receptor beta
Isoflavones
Estrogen Receptor alpha
Metabolites
Bioactivity
Enantiomers
Phytoestrogens
Genistein
Isomers
Estrogen Receptors

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

Cite this

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

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 6, 15.03.2004, p. 1559-1567.

Research output: Contribution to journalArticle

@article{9f7029ff0fdc4cb19af05a6772a87d7c,
title = "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",
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.",
keywords = "ER, Estrogen Receptor, HEC-1, HPLC, High Performance Liquid Chromatography, Human Endometrial Carcinoma Cells-1, RBA, Relative Binding Affinity",
author = "Muthyala, {Rajeev S.} and Ju, {Young H.} and Shubin Sheng and Williams, {Lee D.} and Doerge, {Daniel R.} and Katzenellenbogen, {Benita S} and Helferich, {William G} and Katzenellenbogen, {John A.}",
year = "2004",
month = "3",
day = "15",
doi = "10.1016/j.bmc.2003.11.035",
language = "English (US)",
volume = "12",
pages = "1559--1567",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "6",

}

TY - JOUR

T1 - Equol, a natural estrogenic metabolite from soy isoflavones

T2 - Convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta

AU - Muthyala, Rajeev S.

AU - Ju, Young H.

AU - Sheng, Shubin

AU - Williams, Lee D.

AU - Doerge, Daniel R.

AU - Katzenellenbogen, Benita S

AU - Helferich, William G

AU - Katzenellenbogen, John A.

PY - 2004/3/15

Y1 - 2004/3/15

N2 - 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.

AB - 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.

KW - ER

KW - Estrogen Receptor

KW - HEC-1

KW - HPLC

KW - High Performance Liquid Chromatography

KW - Human Endometrial Carcinoma Cells-1

KW - RBA

KW - Relative Binding Affinity

UR - http://www.scopus.com/inward/record.url?scp=1542319924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542319924&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2003.11.035

DO - 10.1016/j.bmc.2003.11.035

M3 - Article

C2 - 15018930

AN - SCOPUS:1542319924

VL - 12

SP - 1559

EP - 1567

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 6

ER -