title: In vivo activity of the bis-triazole D0870 against drug-susceptible and drug-resistant strains of the protozoan parasite Trypanosoma cruzi.
abstract: We report the in vivo activity of the bis-triazole derivative D0870 against a variety of strains of Trypanosoma cruzi, the causative agent of Chagas' disease, including nitroimidazole/nitrofuran-resistant strains. In both acute and chronic murine models of the disease, treatment with D0870 at < or = 10 mg/kg on alternate days for a total of 20 doses provided 60-100% protection against death, regardless of the drug sensitivity of the infecting strain. In the acute model we obtained 70-100% parasitological cure in seven of the nine strains tested, including one intermediate and two highly drug-resistant strains. D0870 was able to cure 30-45% of animals chronically infected with various strains, including those harbouring the Colombiana strain, among which no cures were obtained with benznidazole. We also found that the anti-T. cruzi activity of D0870 is largely retained even if the hosts are immunosuppressed.
authors.affiliation: Departmento de Parasitología, Instituto de Zoología Tropical, Universidad Central de Venezuela, Caracas 1041, Venezuela.
authors.forename: J
authors.initials: J
authors.lastname: Molina
authors.forename: Z
authors.initials: Z
authors.lastname: Brener
authors.forename: A J
authors.initials: AJ
authors.lastname: Romanha
authors.forename: J A
authors.initials: JA
authors.lastname: Urbina
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004351:Drug Resistance; D005260:Female; D051379:Mice; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D014230:Triazoles; D014344:Trypanocidal Agents; C058219:ICI 195739