Antiretroviral activity of metal-chelating HIV-1 integrase inhibitors

Eur J Med Chem. 2014 Aug 18:83:594-600. doi: 10.1016/j.ejmech.2014.06.055. Epub 2014 Jun 26.

Abstract

Data regarding the activity of metal complexes against HIV virus in cell are surprisingly scarce. In this study, we present the antiviral activity against HIV-infected cells of different types of chelating ligands and of their metal complexes. In particular, the carboxamide chelating scaffold and the corresponding coordination compounds demonstrated an interesting antiviral profile in the nanomolar range. These molecules inhibit not only HIV integrase catalytic activity, but they also interfere with the function of the RNase H component of the HIV reverse transcriptase. Here we also discuss the thermodynamic characterization in solution of the metal complexes of the most active ligands, affording to the best of our knowledge for the first time this type of data for complexes with anti-HIV activity.

Keywords: Antiviral agents; Dual inhibitors; HIV-1 RNase H inhibitors; HIV-1 integrase inhibitors; Metal complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-2 / drug effects
  • Inhibitory Concentration 50
  • Ligands
  • Thermodynamics

Substances

  • Anti-HIV Agents
  • Chelating Agents
  • Coordination Complexes
  • HIV Integrase Inhibitors
  • Ligands
  • HIV Integrase