| Abstract
| - Resveratrol (1) is a polyphenolic natural product, which functions as both a mechanism-based inactivatorand a co-reductant of the COX-1 peroxidase. These functions are mediated through different moieties onthe molecule, namely, the m-hydroquinone moiety (mechanism-based inactivator) and the phenol moiety(co-reductant). Implicit in this bifunctionality is the notion that resveratrol is oxidized at the peroxidaseactive site of COX-1, resulting in the formation of two hypothetical radical species. Oxidation of them-hydroquinone moiety can generate a hypothetical m-semiquinone radical, which is unstabilized andleads to irreversible enzyme inactivation. Oxidation of the phenol moiety can generate a hypotheticalphenoxy radical, which is stabilized and leads to co-reduction during peroxidase catalysis. These tworadicals have been trapped as the resveratrol dimers, cis-ε-viniferin (4, trapped m-semiquinone radical)and trans-δ-viniferin (5, trapped phenoxy radical), and identified by liquid chromatography (LC),absorbance spectroscopy, and LC/tandem mass spectrometry (MSn) methods. Methoxy-resveratrolanalogues, in which either the m-hydroquinone or the phenol moiety were protected as methyl ethers,were used to confirm the proposed mechanism of viniferin production by COX-1.
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