Viniferin formation by COX-1: evidence for radical intermediates during co-oxidation of resveratrol.
Resveratrol (1) is a polyphenolic natural product, which functions as both a mechanism-based inactivator and a co-reductant of the COX-1 peroxidase. These functions are mediated through different moieties on the 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 peroxidase active site of COX-1, resulting in the formation of two hypothetical radical species. Oxidation of the m-hydroquinone moiety can generate a hypothetical m-semiquinone radical, which is unstabilized and leads to irreversible enzyme inactivation. Oxidation of the phenol moiety can generate a hypothetical phenoxy radical, which is stabilized and leads to co-reduction during peroxidase catalysis. These two radicals have been trapped as the resveratrol dimers, cis-epsilon-viniferin (4, trapped m-semiquinone radical) and trans-delta-viniferin (5, trapped phenoxy radical), and identified by liquid chromatography (LC), absorbance spectroscopy, and LC/tandem mass spectrometry (MS(n)) methods. Methoxy-resveratrol analogues, 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.
Szewczuk
Lawrence M
LM
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Lee
Seon Hwa
SH
Blair
Ian A
IA
Penning
Trevor M
TM
D001572:Benzofurans / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D051545:Cyclooxygenase 1; D013058:Mass Spectrometry; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012118:Resorcinols / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001572:Benzofurans; D012118:Resorcinols; D013267:Stilbenes; C477734:delta-viniferin; C091891:epsilon-viniferin; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D000077185:Resveratrol