Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor

Metabolites of methoxychlor such as 2-( p-hydroxyphenyl)-2-( p-methoxyphenyl)-1,1,1-trichloroethane (mono-OH-MXC) and 2,2-bis( p-hydroxyphenyl)-1,1,1-trichloroethane (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which the carbon atom bridging two benzene rings is the ch...

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Bibliographic Details
Published in:	Chemosphere (Oxford) Vol. 54; no. 8; pp. 1273 - 1276
Main Authors:	Miyashita, Masahiro, Shimada, Takahiro, Nakagami, Shizuka, Kurihara, Norio, Miyagawa, Hisashi, Akamatsu, Miki
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-02-2004 Elsevier
Subjects:	Biological and medical sciences Endocrine disruption Estradiol - chemistry Estradiol - metabolism Estrogenic activity Hydrogen bond Medical sciences Metabolic activation Methoxychlor - chemistry Methoxychlor - metabolism Methylation Pesticides, fertilizers and other agrochemicals toxicology Reagent Kits, Diagnostic Receptor binding Receptors, Estrogen - antagonists & inhibitors Receptors, Estrogen - metabolism Stereoisomerism Toxicology Endocrine disruption Metabolic activation Receptor binding Estrogenic activity Hydrogen bond Insecticide Enantioselectivity Metabolite Toxicity Pesticides Estrogen Endocrine disruptor Methoxychlor Isomer Biological fixation Structure activity relation Organochlorine compounds Enantiomer Comparative study Biological receptor
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Summary:	Metabolites of methoxychlor such as 2-( p-hydroxyphenyl)-2-( p-methoxyphenyl)-1,1,1-trichloroethane (mono-OH-MXC) and 2,2-bis( p-hydroxyphenyl)-1,1,1-trichloroethane (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which the carbon atom bridging two benzene rings is the chiral centre. In previous studies the estrogenic activity of racemic mono-OH-MXC has been measured, and the activity of each enantiomer of this compound has not yet been elucidated. In this study, we evaluated the estrogen receptor-binding activity of each enantiomer of mono-OH-MXC to clarify the enantioselective recognition by the estrogen receptor. ( S)-mono-OH-MXC showed 3-fold higher binding activity than that of the ( R) enantiomer. The activity of bis-OH-MXC was only 1.7-fold higher than that of ( S)-mono-OH-MXC. This result suggests that the one hydroxy group and the orientation of the CCl 3 group of mono- and bis-OH-MXCs are important for the interaction with the estrogen receptor. The result also points out the estrogenic activity of methoxychlor after metabolic activation in vivo, which predominantly produces the ( S)-mono-OH-MXC, may be higher than estimated from the in vitro activity of racemic mixtures.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0045-6535 1879-1298
DOI:	10.1016/j.chemosphere.2003.10.035