Tyrosinase-catalyzed oxidation of resveratrol produces a highly reactive ortho-quinone: Implications for melanocyte toxicity.

trans-Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RES), a naturally occurring polyphenol, has recently attracted increased interest as a health-beneficial agent. However, based on its p-substituted phenol structure, RES is expected to be a substrate for tyrosinase and to produce a toxic o-quinone metabolite. The results of this study demonstrate that the oxidation of RES by tyrosinase produces 4-(3',5'-dihydroxy-trans-styrenyl)-1,2-benzoquinone (RES-quinone), which decays rapidly to an oligomeric product (RES-oligomer). RES-quinone was identified after reduction to its corresponding catechol, known as piceatannol. RES-quinone reacts with N-acetylcysteine, a small thiol, to form a diadduct and a triadduct, which were identified by NMR and MS analyses. The production of a triadduct is not common for o-quinones, suggesting a high reactivity of RES-quinone. RES-quinone also binds to bovine serum albumin through its cysteine residue. RES-oligomer can oxidize GSH to GSSG, indicating its pro-oxidant activity. These results suggest that RES could be cytotoxic to melanocytes due to the binding of RES-quinone to thiol proteins.