title: Activity of the new triazole derivative albaconazole against Trypanosoma (Schizotrypanum) cruzi in dog hosts.
abstract: Albaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals. Furthermore, the parasitological, PCR, serological, and proliferative assay results indicated parasitological cure indices of 25 and 100% among animals inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5 mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand, although albaconazole given at 1.5 mg/kg/day was very effective in suppressing the proliferation of the parasite in animals infected with the Berenice-78 T. cruzi strain, no parasitological cure was observed among them, even when a longer treatment period (150 doses) was used. In conclusion, our results demonstrate that albaconazole has trypanocidal activity in vivo and is capable of inducing radical parasitological cure, although natural resistance to this compound was also indicated. Furthermore, the compound can be used in long-term treatment schemes (60 to 150 days) with minimal toxicity and thus represents a potentially useful candidate for the treatment of human Chagas' disease.
authors.affiliation: Departamento Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto. Ouro Preto, Minas Gerais, CEP 35400-000, Brazil. mtbahia@nupeb.ufop.br
authors.forename: Paulo Marcos da Matta
authors.initials: PM
authors.lastname: Guedes
authors.forename: Julio A
authors.initials: JA
authors.lastname: Urbina
authors.forename: Marta
authors.initials: M
authors.lastname: de Lana
authors.forename: Luis C C
authors.initials: LC
authors.lastname: Afonso
authors.forename: Vanja M
authors.initials: VM
authors.lastname: Veloso
authors.forename: Washington L
authors.initials: WL
authors.lastname: Tafuri
authors.forename: George L L
authors.initials: GL
authors.lastname: Machado-Coelho
authors.forename: Egler
authors.initials: E
authors.lastname: Chiari
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000096:biosynthesis; D009000:Monocytes / Q000469:parasitology; D009547:Nifurtimox / Q000627:therapeutic use; D009593:Nitroimidazoles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014230:Triazoles / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi
chemical_list: D007074:Immunoglobulin G; D009593:Nitroimidazoles; D011799:Quinazolines; D014230:Triazoles; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole; C112424:albaconazole