Isoflavonoids from Erythrina poeppigiana: Evaluation of Their Binding Affinity for the Estrogen Receptor

Abstract

Five new isoflavones, named 5,4'-dihydroxy-7-methoxy-3'-(3-methylbuten-2-yl)isoflavone (1), 5,2',4'-trihydroxy-7-methoxy-5'-(3-methylbuten-2-yl)isoflavone (2), 5,4'-dihydroxy-7-methoxy-3'-(3-methyl-2-hydroxybuten-3-yl)isoflavone (3), 3'-formyl-5,4'-dihydroxy-7-methoxyisoflavone (4), and 5-hydroxy-3''-hydroxy-2'',2''-dimethyldihydropyrano[5'',6'':3',4']isoflavone (5), as well as six known compounds, wighteone (6), 3'-isoprenylgenistein (7), isolupabigenin (8), alpinumisoflavone (9), erypoegin D (10), and crystacarpin (11), were isolated from Erythrina poeppigiana. The structures of the isolated compounds were elucidated on the basis of chemical and spectroscopic analysis. The affinity of these compounds for the estrogen receptors ERalpha and ERbeta was evaluated using a receptor binding assay. While isoprenyl and dimethylpyrano substituents in ring A reduced the affinity of binding to ERbeta ca. 100-fold compared to genistein, the isoprenyl substituent in ring B was better accommodated, allowing 7 to bind with ca. 10-fold lower affinity than genistein.

Estrogenic properties of naturally occurring prenylated isoflavones in U2OS human osteosarcoma cells: Structure–activity relationships

“…For example, an isoprenyl moiety at position 6 of 5 was found to be associated with a drastic reduction of genistein affinity to both ERs as reported previously (see additionanl table) [3]. However this seems to have only a minor impact on the transactivation potency of Gen on U2OS cells, since 5 significantly activated the ER-coupled reporter gene expression in both ER␣-and ER␤-dependent test systems (Fig.…”

“…The genistein-related compounds, isopoegin A (5,4 -dihydroxy-7-methoxy-3 -(3-methylbuten-2-yl)isoflavone) (1), isopoegin B (5,2 ,4 -trihydroxy-7-metoxy-5 -(3-methylbuten-2-yl)isoflavone) (2), isopoegin C (5,4 -dihydroxy-7-methoxy-3 -(3-methyl-2-hydroxybuten-3-yl)isoflavone) (3), isopoegin D (5-hydroxy-3 -2 ,2 -dimethylhydropyrano [5 ,6 ,3 ,4 ]isoflavone) (4), wighteone (5) [18], 3 -isoprenylgenistein (6) [19], isolupalbigenin (7) [20] and alpinumisoflavone (8) [21] were isolated from E. poeppigiana [3]. 2.3.…”

“…We recently reported the isolation and characterization of novel and known isoflavonoids from E. poeppigiana, among which eight appear to be structurally related to genistein with isoprenyl and/or 7-methoxy substitution. In addition, significant binding affinities for the two isotypes of the estrogen receptor ER␣ and ER␤ were demonstrated (additional table) [3].…”

“…Hence, the recently isolated naturally occurring derivatives of genistein show that isoprenyl (and 7-methoxy) substitutions may have a profound impact on its bioactivity and thereby change the risk/benefit profile of this compound [3]. As a first step in characterizing these prenylgenistein derivatives, the aim of this work was to assess the consequences of the chemical modification of genistein by prenylation and/or 7-methoxylation on the estrogenicity.…”

Mutagenicidade e estrogenicidade de plantas da família Eriocaulaceae e relação estrutura-atividade de algumas substâncias isoladas

“…Estudos de relação estrutura-atividade de compostos naturais e sintéticos estão sendo cada vez mais estudados com o propósito de identificar e elucidar os mecanismos pelos quais certas substâncias agem (ANTCZAC et al, 2009;CAI et al, 2006;DJIOGUE et al, 2009;THOMPSON et al, 2000;YUAN et al, 2009). …”