title: A new class of phytoestrogens; evaluation of the estrogenic activity of deoxybenzoins.
abstract: 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) ERalpha and ERbeta were found grossly comparable to those of daidzein, some exhibited considerable selectivity and transcriptional bias toward ERbeta, which appeared to allow for enhancement of ER-mediated transcription via deoxybenzoin binding of ERbeta. 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 ERbeta, albeit with different orientations. Our data support the view that deoxybenzoins constitute a promising new class of ERbeta-biased phytoestrogens.
authors.affiliation: Department of Pharmacy, University of Athens Panepistimiopolis Zografou, GR-15771 Athens, Greece.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Fokialakis
authors.forename: George
authors.initials: G
authors.lastname: Lambrinidis
authors.forename: Dimitra J
authors.initials: DJ
authors.lastname: Mitsiou
authors.forename: Nektarios
authors.initials: N
authors.lastname: Aligiannis
authors.forename: Sofia
authors.initials: S
authors.lastname: Mitakou
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mikros
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001573:Benzoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D048789:Phytoestrogens; D028321:Plant Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D004958:Estradiol; C004742:daidzein; D000469:Alkaline Phosphatase; C492807:deoxybenzoin; D001573:Benzoin