| 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 theimportance of the prenyl group for hormonal activity. We investigated the effects of substituting the prenylgroup at C(8) with alkyl chains of varying lengths and branching patterns on estrogen receptor (ER) subtypeERα- and ERβ-binding affinities and transcriptional activities. In addition, features of the ligand-inducedreceptor conformations were explored using a set of specific ER-binding peptides. The new 8-alkylnaringeninswere found to span an activity spectrum ranging from full agonism to partial agonism to antagonism. Moststrikingly, 8-(2,2-dimethylpropyl)naringenin exhibited full agonist character on ERα, but pronouncedantagonist character on ERβ. Knowledge on how ER-subtype-selective activities can be designed providesvaluable information for future drug or tool compound discovery.
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