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Antimicrobial Agents and Chemotherapy, October 2008, p. 3642-3647, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Activity of Hydroxyurea against Leishmania mexicana{triangledown}

Hugo Martinez-Rojano,1,2 Javier Mancilla-Ramirez,1,3 Laura Quiñonez-Diaz,1,4 and Norma Galindo-Sevilla3*

Departamento de Posgrado, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, Mexico,1 Departamento de Urgencias Pediatricas, Hospital de Gineco-Pediatria 3A, IMSS, Mexico City, Mexico,2 Subdireccion de Investigacion Clinica, Instituto Nacional de Perinatologia, Mexico City, Mexico,3 Division Academica de Ciencias de la Salud, Universidad Juarez Autonoma de Tabasco, Villahermosa, Tabasco, Mexico4

Received 28 January 2008/ Returned for modification 26 March 2008/ Accepted 28 July 2008

Leishmania mexicana is a protozoan parasite that causes a disease in humans with frequent relapses after treatment. It is also highly resistant to the currently available drugs. For this reason, there is an urgent need for more effective antileishmanial drugs. Hydroxyurea, an anticancer drug, is toxic to replicating eukaryotic cells and has been proven to be effective in arresting the Leishmania major cell cycle. In this study, hydroxyurea was tested in an in vitro model of intracellular Leishmania infection in macrophages. The parasite density in infected macrophages was measured by microscopy after incubation for various times and treatment with hydroxyurea at different concentrations. Viable parasites that could be transformed into promastigotes by shifting the temperature to 26°C were counted every other day after the replacement of hydroxyurea with fresh medium. Meglumine antimoniate, the standard drug treatment for Leishmania mexicana, was used as a reference drug under the same experimental conditions. Hydroxyurea completely eliminated Leishmania parasites when it was used at a dosage of 10 or 100 µg/ml. Differences in the length of treatment needed to achieve elimination were as follows: the 10-µg/ml doses required 9 days, while 3 days was sufficient when 100 µg/ml was used. Hydroxyurea had a 50% effective dose of 0.015 µg/ml in vitro, which was observed on day 6 after exposure. Hydroxyurea is highly effective in killing intracellular amastigotes in vitro.

* Corresponding author. Mailing address: Instituto Nacional de Perinatologia, Subdireccion de Investigacion Clinica, Torre de Investigacion, 4to. Piso, Montes Urales #800, Col. Lomas de Virreyes, Mexico City 11000, Mexico. Phone: 52 (55) 5520 9900, ext. 513. Fax: 52 (55) 5294 2949. E-mail: NGalindoSevilla{at}hotmail.com

{triangledown} Published ahead of print on 11 August 2008.

Antimicrobial Agents and Chemotherapy, October 2008, p. 3642-3647, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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