A New Class of Phytoestrogens: Evaluation of the Estrogenic Activity of Deoxybenzoins

Although deoxybenzoins are intermediates in the synthesis of isoflavones, their estrogenic activity has not been investigated. Eleven deoxybenzoins were synthesized and their estrogenicity was evaluated. While their affinities for estrogen receptors (ER) ERα and ERβ were found grossly comparable to those of daidzein, some exhibited considerable selectivity and transcriptional bias toward ERβ, which appeared to allow for enhancement of ER-mediated transcription via deoxybenzoin binding of ERβ. Their activity to stimulate the proliferation of ER-positive breast cancer cells and regulate the expression of endogenous and stably transfected reporter genes differed considerably, with some inhibiting cell proliferation while effectively inducing gene expression at the same time. Molecular modeling confirmed that deoxybenzoins fit well in the ligand binding pocket of ERβ, albeit with different orientations. Our data support the view that deoxybenzoins constitute a promising new class of ERβ-biased phytoestrogens.