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
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
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DOI：
10.1016/j.bmc.2003.11.035
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发表时间：
2004-03-15
影响因子：
3.5
通讯作者：
Katzenellenbogen, JA
中科院分区：
文献类型：
--
作者：
Muthyala, RS;Ju, YH;Katzenellenbogen, JA
雌马酚是体内由大豆植物雌激素大豆苷元在肠道菌群作用下产生的代谢物。众所周知，它是雌激素，因此人类接触雌马酚可能会产生显著的生物效应。马雌酚是一种手性分子，可以以r -马雌酚和s -马雌酚的对映体存在。为了研究外消旋(+/-)-马雌酚及其纯对映体的生物活性，我们开发了一种高效、简便的方法，从现有的异lavanoid前体中制备(+/-)-马雌酚。此外，我们优化了一种手性高效液相色谱分离马雌酚对映体的方法，并首次研究了对映体对雌激素受体erα和erβ的活性。在结合实验中，s -雌马酚具有较高的结合亲和力，优先于ERbeta （K-i[ERbeta] = 16 nM; β / α = 13倍），与染料木黄酮（K-i[ERbeta] = 6.7 nM; β / α = 16）相当，而r -雌马酚的结合较弱，优先于erα (K-i[ERalpha] = 50 nM; β / α = 0.29)。所有雌马酚异构体对这两种er的亲和力都高于生物合成前体大豆苷元。马雌酚对映体的可获得性和体外表征将使其生物学效应得到更详细的研究。(C) 2004 Elsevier Ltd.版权所有。
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 isollavanoid 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, ERalpha and ERbeta. In binding assays, S-equol has a high binding affinity, preferential for ERbeta (K-i[ERbeta] = 16 nM; beta/alpha = 13 fold), that is comparable to that of genistein (K-i[ERbeta] = 6.7 nM; beta/alpha= 16), whereas R-equol binds more weakly and with a preference for ERalpha (K-i[ERalpha] = 50 nM; beta/alpha = 0.29). All equol isomers have higher affinity for both ERs than does the biosynthetic precursor daidzein. The availability an the in vitro characterization of the equol enantiomers should enable their biological effects to be studied in detail. (C) 2004 Elsevier Ltd. All rights reserved.