Polyphenols as superoxide dismutase modulators and ligands for estrogen receptors

The capacity of estrogen and stilbene derivatives to modulate the activity of superoxide dismutases in relation with their estrogenic properties has been studied. The properties of trans-resveratrol (3,5,4ʹ-trihydroxystilbene) and its analogues, 4-hydroxystilbene, 4,4ʹdihydroxystilbene, 3,5-dihydroxystilbene, 3,5,4ʹ-trimethoxystilbene and 4,4ʹ-dihydroxy-3,5,3ʹ,5ʹ-tetramethylstilbene were compared to 17(beta)-estradiol and its analogues (2-methoxyestradiol, estrone, 2-hydroxyestradiol and 2-methoxyestrone). Measurement of estrogen receptor-(beta) (ER-(beta)) binding capacity was carried out by a receptor competitor assay associated with fluorescence polarisation detection. The superoxide dismutase (SOD) modulation activity was followed with a spectrophotometric assay using the sequence xanthine/xanthine oxidase-2,3-bis[2-methoxy-4-nitro-sulfo-phenyl]-2H-tetrazolium-5-carboxanilide (X/XO-XTT). The structure–activity relationship was different for the two series tested. In the estrogenic series, a compound which does not inhibit SOD, is recognized by the ER-(beta). In contrast for the stilbenic series both properties are parallel each other.