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Am. J. Trop. Med. Hyg., 80(4), 2009, pp. 568-573
Copyright © 2009 by The American Society of Tropical Medicine and Hygiene

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Effect of Oral Treatment with Pyrazole Carbohydrazide Derivatives against Murine Infection by Leishmania amazonensis

Karen S. Charret, Raquel F. Rodrigues, Alice M. R. Bernardino, Adriana O. Gomes, Adriana V. Carvalho, Marilene M. Canto-Cavalheiro, Leonor Leon, AND Veronica F. Amaral*
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Instituto de Química, Departamento de Química Orgânica, Universidade Federal Fluminense, Programa de Pós-graduação em Química Orgânica, Niterói, Brazil; Instituto de Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Niterói, Brazil

Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO2 and X = NO2/Y = Cl were independently investigated in the CBA mouse model of cutaneous leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohydrazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspartate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against leishmaniasis.

Received July 21, 2008. Accepted for publication September 16, 2008.

Financial support: This work is supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FIOCRUZ, Universidade Federal Fluminense, Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, Programa de Pós-graduação em Química Orgânica, and fellowships from CAPES, Brazil.

* Address correspondence to Veronica F. Amaral, Instituto Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Outeiro de São João Baptista, Valonguinho, CEP 24020-150, Niterói, RJ, Brazil. E-mail: vfa{at}vm.uff.br

Authors’ addresses: Karen S. Charret, Raquel F. Rodrigues, Marilene M. Canto-Cavalheiro, and Leonor Leon, Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil, 4.365 pav. 26 sl. 405, Manguinhos, CEP 21045-900, Rio de Janeiro, RJ, Brazil. Alice M. R. Bernardino and Adriana O. Gomes, Instituto de Química, Departamento de Química Orgânica, Universidade Federal Fluminense, Programa de Pós-graduação em Química Orgânica, Outeiro de São João Baptista, CEP 24020-150, Niterói, RJ, Brazil. Adriana V. Carvalho and Veronica F. Amaral, Instituto Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Outeiro de São João Baptista, Valonguinho, CEP 24020-150, Niterói, RJ, Brazil.






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Copyright © 2009 by the American Society of Tropical Medicine and Hygiene.