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JAC Advance Access published online on July 19, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl259
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received February 16, 2006
Revised May 26, 2006
Accepted May 29, 2006

Original article

Trypanocidal activity of the phenyl-substituted analogue of furamidine DB569 against Trypanosoma cruzi infection in vivo

Elen M. de Souza 1, Gabriel M. Oliveira 1, David W. Boykin 2, Arvind Kumar 2, Qiyue Hu 2, and Maria De Nazaré C. Soeiro 1 *

1 Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brasil
2 Department of Chemistry, Georgia State University, Atlanta, USA

* To whom correspondence should be addressed.
Maria De Nazaré C. Soeiro, E-mail: soeiro{at}ioc.fiocruz.br


  Abstract

Objectives: Aromatic diamidines have been successfully used to combat a wide range of parasites that cause important human infections. One such compound is furamidine (DB75) and we recently reported that one of its analogues, an N-phenyl analogue (DB569), exhibits higher trypanocidal dose and time-dependent effects against different forms of Trypanosoma cruzi as compared with DB75. Our present aim was to investigate the efficacy of DB569 in a T. cruzi mouse model.

Methods: The trypanocidal activity of the compound was evaluated by clinical, parasitological, histopathological and biochemical investigations.

Results: Treatment with DB569 significantly reduced cardiac parasitism, partially increased the survival rates of mice and lowered the levels of alanine aminotransferase and creatinine indicating a protective role against renal and hepatic lesions caused by the parasite infection.

Conclusions: Altogether, the data support the potential effect of this class of compounds against T. cruzi and motivate the screening of new diamidines for efficacy against Chagas' disease.

Keywords: aromatic diamidines; therapy; infected mice; Chagas' disease.
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