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

doi:10.1016/j.bmcl.2012.08.108

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 journal › Article › peer-review

93 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 language	English (US)
Pages (from-to)	6642-6646
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2012.08.108
State	Published - 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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antiviral
Decitabine
HIV-1
Mutagenesis
Resveratrol

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10.1016/j.bmcl.2012.08.108

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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.",

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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). ",

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AU - Clouser, Christine L.

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AU - Zhou, Ding

AU - Dimick-Gray, Sarah

AU - Mansky, Louis M.

AU - Patterson, Steven E.

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N2 - 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.

AB - 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.

KW - Antiviral

KW - Decitabine

KW - HIV-1

KW - Mutagenesis

KW - Resveratrol

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

Abstract

Bibliographical note

UN SDGs

Keywords

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