title: Resveratrol analogs: promising chemopreventive agents.
abstract: Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol.
authors.affiliation: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720, USA.
authors.forename: Talysa
authors.initials: T
authors.lastname: Ogas
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; D000077185:Resveratrol
keywords: chemoprevention; combination; derivatives; metabolites; resveratrol; synergy