Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites.

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Hoshino J, Park EJ, Kondratyuk TP, Marler L, Pezzuto JM, van Breemen RB, Mo S, Li Y, Cushman M

Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites.

J Med Chem. 2010 Jul 8;53(13):5033-43. doi: 10.1021/jm100274c.

PubMed ID
20527891 [ View in PubMed
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Abstract

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF) alpha induced NFkappaB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, proliferation of KB or MCF7 cells, induction of quinone reductase 1 (QR1), accumulation in the sub-G(1) phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QR1 induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities and the 4'-sulfate inhibited NFkappaB induction, as well as COX-1 and COX-2 activities. Resveratrol and its 3'-sulfate and 4-sulfate inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ResveratrolProstaglandin G/H synthase 2IC 50 (nM)750N/AN/ADetails