1NM-PP1 treatment of mice infected with Toxoplasma gondii

J Vet Med Sci. 2011 Oct;73(10):1377-9. doi: 10.1292/jvms.11-0085. Epub 2011 Jun 16.

Abstract

Bumped kinase inhibitors (BKIs) target analog-sensitive kinases, which the genomes of mammals rarely encode. Previously, we demonstrated that a BKI effectively suppressed the in vitro replication of Toxoplasma gondii, the causative pathogen of toxoplasmosis, by targeting T. gondii calcium-dependent protein kinase 1 (TgCDPK1) (Eukaryotic Cell, 9: 667-670). Here, we examined whether the BKI 1NM-PP1 reduced parasite replication in vivo. A high dose of 1NM-PP1, by intraperitoneal injection, just before the parasite inoculation effectively reduced the parasite load in the brains, livers, and lungs of T. gondii-infected mice, however, a low dose of 1NM-PP1 with oral administration didn't change the survival rates of infected mice.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiprotozoal Agents / therapeutic use*
  • Brain / parasitology
  • Dose-Response Relationship, Drug
  • Female
  • Injections, Intraperitoneal
  • Liver / parasitology
  • Lung / parasitology
  • Mice
  • Mice, Inbred ICR
  • Parasite Load
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Survival Rate
  • Toxoplasmosis / drug therapy*
  • Toxoplasmosis / mortality
  • Toxoplasmosis / parasitology

Substances

  • 1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine
  • Antiprotozoal Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines