Tetra-chloro-(bis-(3,5-dimethylpyrazolyl)methane)gold(III) chloride: An HIV-1 reverse transcriptase and protease inhibitor

J Inorg Biochem. 2009 Feb;103(2):190-4. doi: 10.1016/j.jinorgbio.2008.10.001. Epub 2008 Oct 14.

Abstract

The title compound ([3,5-Me(2)bpzaH(2)][AuCl(4)]Cl, 1) (Me(2)bpza=bis(3,5-dimethylpyrazolyl)acetic acid), was prepared by reacting H[AuCl(4)] with 3,5-Me(2)bpza; and spectroscopically and structurally characterized. In the solid state structure of 1, the pyrazolyl ligand is doubly protonated to form two strong charge assisted hydrogen bonds of the type N(+)Hcdots, three dots, centeredCl(-) with the single chloride anion whilst the [AuCl(4)](-) anion remains discrete. The anti-HIV-1 activity of 1 was determined by a colorimetric direct enzyme reverse transcriptase (RT) assay and a fluorogenic protease (PR) assay. Compound 1 significantly (p<0.05) inhibited RT over a concentration range of 5-250muM and inhibited HIV-1 protease at 100muM. Compound 1 inhibited two very important HIV-1 enzymes (RT and PR) in direct enzyme assays and therefore warrants further evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Crystallography, X-Ray
  • HIV Protease / drug effects*
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry*
  • Organogold Compounds / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology*

Substances

  • HIV Protease Inhibitors
  • Organogold Compounds
  • Reverse Transcriptase Inhibitors
  • tetrachloro(bis(3,5-dimethylpyrazolyl)methane)gold(III)
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • HIV Protease