Synthesis and biological properties of new stilbene derivatives of resveratrol as new selective aryl hydrocarbon modulators.

Philippe de Médina (1) , Robert Casper (2) , Jean-François Savouret (3) , Marc E. Poirot (1)

1 Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique
2 Samuel Lunenfeld Research Institute
3 UMR-S-530 - Physiologie cellulaire des régulations hormonale, nutritionnelles et pharmacologiques

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.

Domaines: Sciences pharmaceutiques

Philippe de Médina, Robert Casper, Jean-François Savouret, Marc E. Poirot. Synthesis and biological properties of new stilbene derivatives of resveratrol as new selective aryl hydrocarbon modulators.. Journal of Medicinal Chemistry, 2005, 48, pp.287-91. ⟨10.1021/jm0498194⟩. ⟨inserm-00090771⟩