The efficacy of an N-substituted imidazole, RS-49676, against a Trypanosoma cruzi infection in mice.

Abstract

In vitro studies against epimastigotes and intracellular amastigotes and in vivo studies in inbred C3H/He mice infected with Trypanosoma cruzi Brazil strain were performed to determine the activities of two N-substituted imidazole compounds, RS-49676 and ketoconazole. Both compounds are extremely active in vitro against the amastigotes (ED50 less than 0.0001 micrograms/ml) yet inactive against the epimastigotes. In vivo, RS-49676 increased the mean survival time over 11 weeks beyond the untreated control when given subcutaneously twice daily at 100 mg/kg/day. Ketoconazole increased the mean survival time 11-18 days beyond the untreated control (mean survival time 22 days) when given subcutaneously twice daily at 100 mg/kg or orally once daily at 100 mg/kg. Approximately 20%-25% of the RS-49676 treated mice were cured as determined by culturing the blood of infected mice with fibroblast lung cells. None of the ketoconazole mice were cured.

• Authors: V R Scott, T R Matthews
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 37 Issue 2 Pg. 308-13 (Sep 1987) ISSN: 0002-9637 [Print] United States
• PMID: 3116868 (Publication Type: Journal Article)

Chemical References

• Trypanocidal Agents
• RS 49676
• Ketoconazole

Topics

• Animals
• Chagas Disease (drug therapy)
• Chemical Phenomena
• Chemistry
• Female
• Ketoconazole (analogs & derivatives, therapeutic use)
• Mice
• Mice, Inbred C3H
• Trypanocidal Agents (therapeutic use)
• Trypanosoma cruzi (drug effects)