New 2-arylnaphthalenediols and triol inhibitors of HIV-1 integrase--discovery of a new polyhydroxylated antiviral agent

Bioorg Med Chem. 2010 Jul 15;18(14):5194-201. doi: 10.1016/j.bmc.2010.05.059. Epub 2010 May 26.

Abstract

A series of 13 hydroxylated 2-arylnaphthalenes have been synthesized and evaluated as HIV-1 integrase inhibitors. 7-(3,4,5-trihydroxyphenyl)naphthalene-1,2,3-triol 1c revealed chemical instability upon storage, leading to the isolation of a dimer 5c which was also tested. In the 2-arylnaphthalene series, all compounds were active against HIV-1 IN with IC50's within the 1-10 microM range, except for 1c and 5c which displayed submicromolar activity. Antiviral activity against HIV-1 replication was measured on 1b-c and 5c. Amongst the tested molecules, only 5c was found to present antiviral properties with a low cytotoxicity on two different cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry*
  • Naphthalenes / pharmacology*

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Naphthalenes