title: Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine.
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.
authors.affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA. cclouser@umn.edu
authors.forename: Christine L
authors.initials: CL
authors.lastname: Clouser
authors.forename: Jay
authors.initials: J
authors.lastname: Chauhan
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Bess
authors.forename: Jessica L
authors.initials: JL
authors.lastname: van Oploo
authors.forename: Ding
authors.initials: D
authors.lastname: Zhou
authors.forename: Sarah
authors.initials: S
authors.lastname: Dimick-Gray
authors.forename: Louis M
authors.initials: LM
authors.lastname: Mansky
authors.forename: Steven E
authors.initials: SE
authors.lastname: Patterson
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D013267:Stilbenes; D000077209:Decitabine; D001374:Azacitidine; D000077185:Resveratrol