The efficacy of an N-substituted imidazole, RS-49676, against a Trypanosoma cruzi infection in mice.
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.
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
D014344:Trypanocidal Agents; C053704:RS 49676; D007654:Ketoconazole