title: Structural properties of estrogen receptor ligand obtained by study of hydroxylated phthalate ester derivatives.
abstract: Phthalate esters (PEs), a group of plasticizers, are suspected to be endocrine-disrupting chemicals. Here, PE derivatives were used as probes for elucidating the structural properties of estrogen receptor (ER) ligands. A comprehensive study was performed using more than 40 PE derivatives including ring-/alkyl-hydroxylated and nonsymmetrical diesters possessing independently altered alkyls of C1-C8. Estrogenic activity of these derivatives is determined with three assays for ER-binding, coactivator-recruiting and transactivation. Phenolic hydroxylation increased activity, while hydroxylation of the ester alkyl group had no distinct effect on ER binding or transcription coactivator recruitment. Ring-hydroxylated PE derivatives harboring different ester alkyls revealed that the length of both alkyls independently affects transactivation of ER. These comprehensive data would be useful for the better understanding of structure-activity relationship of endocrine-disrupting chemicals.
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Rena
authors.initials: R
authors.lastname: Kusu
authors.forename: Chitose
authors.initials: C
authors.lastname: Toda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.forename: Nakao
authors.initials: N
authors.lastname: Kojima