In vitro and in vivo activities of 1-hydroxy-2-alkyl-4(1H)quinolone derivatives against Toxoplasma gondii

Antimicrob Agents Chemother. 2010 Jan;54(1):517-21. doi: 10.1128/AAC.01001-09. Epub 2009 Nov 2.

Abstract

1-Hydroxy-2-dodecyl-4(1H)quinolone (HDQ) was recently identified as a Toxoplasma gondii inhibitor. We describe here two novel 1-hydroxyquinolones, which displayed 50% inhibitory concentrations 10- and 5-fold lower than that of HDQ. In a mouse model of acute toxoplasmosis, these two compounds and HDQ reduced the percentages of infected peritoneal cells and decreased the parasite loads in lungs and livers. Compound B showed a tendency toward lowering parasite loads in brains in a mouse model of toxoplasmic encephalitis.

MeSH terms

  • Animals
  • Antiparasitic Agents / pharmacology*
  • Antiparasitic Agents / therapeutic use
  • Cells, Cultured
  • DNA, Protozoan / analysis
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / parasitology
  • Flow Cytometry
  • Humans
  • Liver / chemistry
  • Liver / parasitology
  • Lung / chemistry
  • Lung / parasitology
  • Mice
  • Peritoneal Cavity / cytology
  • Peritoneal Cavity / parasitology
  • Quinolones / pharmacology*
  • Quinolones / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toxoplasma / drug effects*
  • Toxoplasmosis, Animal / drug therapy*
  • Toxoplasmosis, Animal / parasitology
  • Toxoplasmosis, Cerebral / drug therapy
  • Toxoplasmosis, Cerebral / parasitology

Substances

  • Antiparasitic Agents
  • DNA, Protozoan
  • Quinolones