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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Aromatase / metabolism
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Biphenyl Compounds / antagonists & inhibitors
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Biphenyl Compounds / metabolism
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Cell Survival / drug effects
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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HL-60 Cells
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Humans
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Inhibitory Concentration 50
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Macrophages / drug effects
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Macrophages / metabolism
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Magnetic Resonance Spectroscopy
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Mice
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NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors
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NAD(P)H Dehydrogenase (Quinone) / metabolism
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism
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Picrates / antagonists & inhibitors
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Picrates / metabolism
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Resveratrol
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Spectrometry, Mass, Electrospray Ionization
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Spectroscopy, Fourier Transform Infrared
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Stilbenes / chemistry*
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Stilbenes / metabolism
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Stilbenes / pharmacology*
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Sulfuric Acid Esters / chemical synthesis
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Sulfuric Acid Esters / chemistry*
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Sulfuric Acid Esters / pharmacology*
Substances
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Antineoplastic Agents
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Biphenyl Compounds
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Enzyme Inhibitors
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NF-kappa B
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Picrates
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Stilbenes
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Sulfuric Acid Esters
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1,1-diphenyl-2-picrylhydrazyl
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Nitric Oxide Synthase
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Aromatase
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Cyclooxygenase 1
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Cyclooxygenase 2
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NAD(P)H Dehydrogenase (Quinone)
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Resveratrol