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In vitro and in vivo activity of the chloroaryl-substituted imidazole viniconazole against Trypanosoma cruzi

Published online by Cambridge University Press:  22 October 2013

CRISTIANE FRANÇA DA SILVA ,
DENISE DA GAMA JAEN BATISTA ,
MARCOS MEUSER BATISTA ,
JESSICA LIONEL ,
ERICA RIPOLL HAMMER ,
RETO BRUN  and
MARIA DE NAZARÉ CORREIA SOEIRO
CRISTIANE FRANÇA DA SILVA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
DENISE DA GAMA JAEN BATISTA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
MARCOS MEUSER BATISTA
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
JESSICA LIONEL
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
ERICA RIPOLL HAMMER
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
RETO BRUN
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
MARIA DE NAZARÉ CORREIA SOEIRO*
Affiliation:
Laboratório de Biologia Celular do Instituto, Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brasil
*
*Corresponding author: Laboratory of Cellular Biology, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365 Manguinhos, Rio de Janeiro, Brazil. E-mail: soeiro@ioc.fiocruz.br
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Summary

Chagas disease (CD) is caused by the intracellular protozoan parasite Trypanosoma cruzi and affects more than 10 million people in poor areas of Latin America. There is an urgent need for alternative drugs with better safety, broader efficacy, lower costs and shorter time of administration. Thus the biological activity of viniconazole, a chloroaryl-substituted imidazole was investigated using in vitro and in vivo screening models of T. cruzi infection. Ultrastructural findings demonstrated that the most frequent cellular damage was associated with plasma membrane (blebs and shedding events), Golgi (swelling aspects) and the appearance of large numbers of vacuoles suggesting an autophagic process. Our data demonstrated that although this compound is effective against bloodstream and intracellular forms (16 and 24 μm, respectively) in vitro, it does not present in vivo efficacy. Due to the urgent need for novel agents against T. cruzi, the screening of natural and synthetic products must be further supported with the aim of finding more selective and affordable drugs for CD.

Keywords

Chagas diseaseTrypanosoma cruzichloroaryl-substituted imidazoleviniconazoleexperimental chemotherapyin vivoin vitro
Type
Research Article
Information
Parasitology , Volume 141 , Issue 3 , March 2014 , pp. 367 - 373
Copyright
Copyright © Cambridge University Press 2013 

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