title: Resveratrol derivatives as promising chemopreventive agents with improved potency and selectivity.
abstract: METHODS
  Despite scores of investigations, the actual impact of resveratrol (3,5,4'-trihydroxy-trans-stilbene) on human health, as a dietary component or supplement, remains moot. This is due to many factors, such as relatively low potency, pleiotropic mechanisms, and rapid metabolism. Nonetheless, as a promiscuous molecule that interacts with numerous targets, resveratrol can be viewed as a scaffold for designing structural relatives potentially capable of mediating more intense responses with greater mechanistic stringency.
  
  
  RESULTS
  We currently report the synthesis and biological evaluation of 92 stilbene analogs. The compounds were tested with in vitro assays for activation of quinone reductase 1, inhibition of quinone reductase 2, nitric oxide production, aromatase, NFκB, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase, or cyclooxygenase-1 and -2, quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, interaction with estrogen receptors, and as antiproliferative agents. Several compounds were found to mediate responses with much greater potency than resveratrol; some mediated pleiotropic responses, as is the case with the parent molecule, but others were highly specific or totally inactive. When administered to rats, higher serum concentrations and greater stability was demonstrated with prototype lead molecules.
  
  
  CONCLUSIONS
  Owing to structural simplicity, facile syntheses are available for large-scale production. These data support the promise of more advanced development of novel resveratrol derivatives as drug entities.
authors.affiliation: College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720, USA.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Laura E
authors.initials: LE
authors.lastname: Marler
authors.forename: Soyoun
authors.initials: S
authors.lastname: Ahn
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Choi
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Juma
authors.initials: J
authors.lastname: Hoshino
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Jermihov
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
authors.forename: Clinton J
authors.initials: CJ
authors.lastname: Grubbs
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000494:pharmacology; D018938:Caco-2 Cells; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D047072:Aromatase Inhibitors; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D013267:Stilbenes; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D000077185:Resveratrol