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Titolo:
Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens
Autore:
Fang, H; Tong, WD; Shi, LM; Blair, R; Perkins, R; Branham, W; Hass, BS; Xie, Q; Dial, SL; Moland, CL; Sheehan, DM;
Indirizzi:
ROW Sci Inc, Jefferson, AR 72079 USA ROW Sci Inc Jefferson AR USA 72079ROW Sci Inc, Jefferson, AR 72079 USA Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 icol, Jefferson, AR 72079 USA
Titolo Testata:
CHEMICAL RESEARCH IN TOXICOLOGY
fascicolo: 3, volume: 14, anno: 2001,
pagine: 280 - 294
SICI:
0893-228X(200103)14:3<280:SRFALD>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BINDING-SITE; IN-VITRO ASSAYS; POLYCHLORINATED HYDROXYBIPHENYLS; INDUCTION; CHEMICALS; LIGANDS; ANALOGS; IDENTIFICATION; METABOLITES; AFFINITIES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Tong, WD ROW Sci Inc, 3900 NCTR Rd,MC 910, Jefferson, AR 72079 USA ROW SciInc 3900 NCTR Rd,MC 910 Jefferson AR USA 72079 72079 USA
Citazione:
H. Fang et al., "Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens", CHEM RES T, 14(3), 2001, pp. 280-294

Abstract

Understanding structural requirements for a chemical to exhibit estrogen receptor (ER) binding has been important in various fields. This knowledge has been directly and indirectly applied to design drugs for human estrogen replacement therapy, and to identify estrogenic endocrine disrupters. This paper reports structure-activity relationships (SARs) based on a total of 230 chemicals, including both natural and xenoestrogens. Activities were generated using a validated ER competitive binding assay, which covers a 10(6)-fold range. This study is focused on identification of structural commonalities among diverse ER ligands. It provides an overall picture of how xenoestrogens structurally resemble endogenous 17 beta -estradiol (E-2) and the synthetic estrogen diethylstilbestrol (DES). On the basis of SAR analysis, five distinguishing criteria were found to be essential for xenoestrogen activity, using E-2 as a template: (1) H-bonding ability of the phenolic ringmimicking the 3-OH, (2) H-bond donor mimicking the 17 beta -OH and O-O distance between 3- and 17 beta -OH, (3) precise steric hydrophobic centers mimicking steric 7 alpha- and 11 beta -substituents, (4) hydrophobicity, and (5) a ring structure. The S-position H-bonding ability of phenols is a significant requirement for ER binding. This contributes as both a H-bond donorand acceptor, although predominantly as a donor. However, the 17 beta -OH contributes as a H-bond donor only. The precise space (the size and orientation) of steric hydrophobic bulk groups is as important as a 17 beta -OH. Where a direct comparison can be made, strong estrogens tend to be more hydrophobic, A rigid ring structure favors ER binding. The knowledge derived from this study is rationalized into a set of hierarchical rules that will beuseful in guidance for identification of potential estrogens.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 15:55:46