摘要：We previously reported that trans -stilbene is metabolically activated to estrogenic compounds by a liver microsomal enzyme system. In this study, we demonstrated the structural requirement for estrogenic activity of various stilbene derivatives including proestrogens. High estrogenic activity in 4,4′-dihydroxystilbene, 4-amino-4′-hydroxystilbene, 4,4′-dihydroxy- α -methylstilbene, hexestrol, and diethylstilbestrol (DES), moderate activity in 4-hydroxystilbene, 4-aminostilbene, 4-hydroxyazobenzene, and 4-hydroxy-4′-nitrostilbene, low activity in 4-nitrostilbene, 4,4′-dihydroxydibenzyl, resveratrol, and 4-hydroxy- α -methylstyrene, and marginal activity in 4,4′-dimethoxystilbene and 4-hydroxymethylstilbene were observed in an estrogen reporter assay using the estrogen-responsive human breast cancer cell line MCF-7 and a binding assay with rat uterus estrogen receptor. In contrast, α -methylstilbene, 4,4′-dimethoxystilbene, 4-hydroxymethylstilbene, dibenzyl, tolan and azobenzene also exhibited estrogenic activities after incubation with liver microsomes of 3-methylcholanthrene- or phenobarbital-treated rats in the presence of NADPH. These results suggest that the structural requirements for the estrogenic activities of stilbene derivatives are a p -hydroxyl group in the A-phenyl ring, vinyl linkage, and a B-phenyl ring for the maximal activity, and hydrophobicity of the linkage for higher activity as observed in DES. p -Nitro and amino groups in the A-phenyl ring are also effective for the estrogenic activity.
关键词：stilbene derivative;estrogenic activity;structure-activity relationship;stilbene-proestrogen;human breast cancer cell MCF-7
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