Synthesis and biological properties of new stilbene derivatives of resveratrol as new selective aryl hydrocarbon modulators.
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.
de Medina
Philippe
P
INSERM U 563, Centre de Physiopathologie de Toulouse Purpan, Innovation Thérapeutique et Oncologie Moléculaire, Institut Claudius Regaud, 20-24 rue du Pont Saint Pierre, 31052 Toulouse Cedex, France.
Casper
Robert
R
Savouret
Jean-François
JF
Poirot
Marc
M
D000818:Animals; D001671:Biochemistry / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011817:Rabbits; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D011959:Receptors, Estradiol / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018675:Toxicity Tests; D015533:Transcriptional Activation / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011959:Receptors, Estradiol; D013267:Stilbenes; D004958:Estradiol; D015500:Chloramphenicol O-Acetyltransferase; D000077185:Resveratrol