title: Identification of xenoestrogens in food additives by an integrated in silico and in vitro approach.
abstract: In the search for xenoestrogens within food additives, we have analyzed the Joint FAO-WHO expert committee database, containing 1500 compounds, using an integrated in silico and in vitro approach. This analysis identified 31 potential estrogen receptor alpha ligands that were reduced to 13 upon applying a stringent filter based on ligand volume and binding mode. Among the 13 potential xenoestrogens, four were already known to exhibit an estrogenic activity, and the other nine were assayed in vitro, determining the binding affinity to the receptor and biological effects. Propyl gallate was found to act as an antagonist, and 4-hexylresorcinol was found to act as a potent transactivator; both ligands were active at nanomolar concentrations, as predicted by the in silico analysis. Some caution should be issued for the use of propyl gallate and 4-hexylresorcinol as food additives.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Parma, 43100 Parma, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Amadasi
authors.forename: Andrea
authors.initials: A
authors.lastname: Mozzarelli
authors.forename: Clara
authors.initials: C
authors.lastname: Meda
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.forename: Pietro
authors.initials: P
authors.lastname: Cozzini
mesh_terms: D000818:Animals; D002460:Cell Line; D016208:Databases, Factual; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry*; D005503:Food Additives / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D011435:Propyl Gallate / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000737:chemistry* / Q000633:toxicity
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D005503:Food Additives; D008024:Ligands; D015262:Xenobiotics; D011435:Propyl Gallate