Abstract
We developed new stilbene derivatives of resveratrol (E)-1-(4'-hydroxyphenyl)-2-(3,5-dihydroxyphenyl)ethene) selective for AhR and devoid of affinity for ER. Among the 24 stilbenes synthesized, all display a higher affinity than resveratrol for AhR. (E)-1-(4'-Trifluoromethylphenyl)-2-(3,5-ditrifluoromethylphenyl)ethene (4e), (E)-1-(4'-methoxyphenyl)-2-(3,5-dichlorophenyl)ethene (4j), and (E)-1-(4'-chlorophenyl)-2-(3,5-dichlorophenyl)ethene (4b) are selective, high-affinity AhR antagonists with, respective, K(i)s of 2.1, 1.4, and 1.2 nM. (E)-1-(4'-Trifluoromethylphenyl)-2-(3,5-dichlorophenyl)ethene (4i) displays a K(i) of 0.2 nM and is a selective and high-affinity agonist on AhR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biochemistry / methods
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Cell Line
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Cells, Cultured
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Chloramphenicol O-Acetyltransferase / drug effects
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Chloramphenicol O-Acetyltransferase / genetics
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Estradiol / pharmacology
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Humans
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Polychlorinated Dibenzodioxins / pharmacology
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Rabbits
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Receptors, Aryl Hydrocarbon / agonists
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Receptors, Aryl Hydrocarbon / antagonists & inhibitors
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Receptors, Aryl Hydrocarbon / drug effects*
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Receptors, Aryl Hydrocarbon / metabolism
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Receptors, Estradiol / drug effects
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Resveratrol
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Stilbenes / chemistry*
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Stilbenes / metabolism
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Stilbenes / pharmacology
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Toxicity Tests
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Transcriptional Activation / drug effects
Substances
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Polychlorinated Dibenzodioxins
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Receptors, Aryl Hydrocarbon
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Receptors, Estradiol
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Stilbenes
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Estradiol
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Chloramphenicol O-Acetyltransferase
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Resveratrol