Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen receptors alpha and beta.
J Med Chem
; 49(25): 7357-65, 2006 Dec 14.
Article
en En
| MEDLINE
| ID: mdl-17149865
ABSTRACT
In search of therapeutic agents for estrogen-related pathologies, phytoestrogens are being extensively explored. In contrast to naringenin, 8-prenylnaringenin is a potent hop-derived estrogenic compound, highlighting the importance of the prenyl group for hormonal activity. We investigated the effects of substituting the prenyl group at C(8) with alkyl chains of varying lengths and branching patterns on estrogen receptor (ER) subtype ERalpha- and ERbeta-binding affinities and transcriptional activities. In addition, features of the ligand-induced receptor conformations were explored using a set of specific ER-binding peptides. The new 8-alkylnaringenins were found to span an activity spectrum ranging from full agonism to partial agonism to antagonism. Most strikingly, 8-(2,2-dimethylpropyl)naringenin exhibited full agonist character on ERalpha, but pronounced antagonist character on ERbeta. Knowledge on how ER-subtype-selective activities can be designed provides valuable information for future drug or tool compound discovery.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Flavanonas
/
Receptor alfa de Estrógeno
/
Receptor beta de Estrógeno
/
Fitoestrógenos
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Bélgica