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Antimicrobial Agents and Chemotherapy, November 2004, p. 4286-4292, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4286-4292.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activity of the New Triazole Derivative Albaconazole against Trypanosoma (Schizotrypanum) cruzi in Dog Hosts

Paulo Marcos da Matta Guedes,1 Julio A. Urbina,2 Marta de Lana,3 Luis C. C. Afonso,1 Vanja M. Veloso,1 Washington L. Tafuri,1 George L. L. Machado-Coelho,4 Egler Chiari,5 and Maria Terezinha Bahia1*

Departamento de Ciências Biológicas,1 Departamento de Análises Clínicas,3 Departamento de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto,4 Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil,5 Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela2

Received 25 March 2004/ Returned for modification 8 June 2004/ Accepted 20 July 2004

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.

* Corresponding author. Mailing address: Departamento Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto. Ouro Preto, Minas Gerais, CEP 35400-000, Brazil. Phone: 55-31-3550.1690. Fax: 55-31-3559.1689. E-mail: mtbahia{at}nupeb.ufop.br.

Antimicrobial Agents and Chemotherapy, November 2004, p. 4286-4292, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4286-4292.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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