Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine

Christine L. Clouser, Jay Chauhan, Matthew A. Bess, Jessica L.Van Oploo, Ding Zhou, Sarah Dimick-Gray, Louis M. Mansky, Steven E. Patterson

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Ribonucleotide reductase inhibitors enhance the anti-HIV-1 activities of a variety of nucleoside analogs, including those that act as chain terminators and those that increase the HIV-1 mutation rate. However the use of these ribonucleotide reductase inhibitors is limited by their associated toxicities. The hydroxylated phytostilbene resveratrol has activity in a host of systems including inhibition of ribonucleotide reductase and has minimal toxicity. Here we synthesized derivatives of resveratrol and examined them for anti-HIV-1 activity and their ability to enhance the antiviral activity of decitabine, a nucleoside analog that decreases viral replication by increasing the HIV-1 mutation rate. The data demonstrates that six of the derivatives have anti-HIV-1 activity greater than resveratrol. However, only resveratrol acted in synergy with decitabine to inhibit HIV-1 infectivity. These results reveal novel resveratrol derivatives with anti-HIV-1 activity that may have mechanisms of action that differ from the drugs currently used to treat HIV-1.

Original languageEnglish (US)
Pages (from-to)6642-6646
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2012

Bibliographical note

Funding Information:
This research was supported by a University of Minnesota Academic Health Center Translational Research Grant as well as by NIH Grant GM56615. C.L.C. was supported in part from NIH Grant T32 CA09138 (Cancer Biology Training Grant); M.A.B. was supported in part from NIH Grant T32 GM008700 (Chemistry-Biology Interface Training Grant).

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Antiviral
  • Decitabine
  • HIV-1
  • Mutagenesis
  • Resveratrol

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