Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor
| Autor: | Miki Akamatsu, Hisashi Miyagawa, Shizuka Nakagami, Masahiro Miyashita, Takahiro Shimada, Norio Kurihara |
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| Rok vydání: | 2004 |
| Předmět: |
Environmental Engineering
medicine.drug_class Stereochemistry Health Toxicology and Mutagenesis Metabolite Estrogen receptor Stereoisomerism Methylation chemistry.chemical_compound medicine Environmental Chemistry Receptor Estradiol Public Health Environmental and Occupational Health Enantioselective synthesis Methoxychlor General Medicine General Chemistry Pollution Receptors Estrogen chemistry Estrogen Reagent Kits Diagnostic Enantiomer |
| Zdroj: | Chemosphere. 54:1273-1276 |
| ISSN: | 0045-6535 |
| DOI: | 10.1016/j.chemosphere.2003.10.035 |
| Popis: | 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 CCl3 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. |
| Databáze: | OpenAIRE |
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