Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment
Mem. Inst. Oswaldo Cruz
; 113(3): 153-160, Mar. 2018. graf
Artigo
em Inglês
| LILACS
| ID: biblio-894905
Biblioteca responsável:
BR1.1
ABSTRACT
BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz) with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
/
Doenças Negligenciadas
/
ODS3 - Meta 3.3 Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
Problema de saúde:
Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
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Doença de Chagas
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Doenças Negligenciadas
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Doença de Chagas
Base de dados:
LILACS
Assunto principal:
Triose-Fosfato Isomerase
/
Trypanosoma cruzi
/
Nitroimidazóis
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2018
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Uruguai
Instituição/País de afiliação:
Universidad de la República/UY