2. Academic Validation
  3. Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites

Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites

  • J Med Chem. 2010 Jul 8;53(13):5033-43. doi: 10.1021/jm100274c.
Juma Hoshino 1,  Eun-Jung Park,  Tamara P Kondratyuk,  Laura Marler,  John M Pezzuto,  Richard B van Breemen,  Shunyan Mo,  Yongchao Li,  Mark Cushman
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences and the Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA.
PMID: 20527891 DOI: 10.1021/jm100274c
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.

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