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Title of the item:

Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment

Title :
Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment
Authors :
Elena Aguilera
Javier Varela
Elva Serna
Susana Torres
Gloria Yaluff
Ninfa Vera de Bilbao
Hugo Cerecetto
Guzmán Alvarez
Mercedes González
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Subject Terms :
Chagas disease
synergism
isobologram
in vivo studies
Arctic medicine. Tropical medicine
RC955-962
Microbiology
QR1-502
Source :
Memórias do Instituto Oswaldo Cruz., Vol 113, Iss 3, Pp 153-160
Publisher :
Instituto Oswaldo Cruz, Ministério da Saúde.
Collection :
LCC:Arctic medicine. Tropical medicine
LCC:Microbiology
Document Type :
article
File Description :
electronic resource
Language :
English
ISSN :
1678-8060
0074-0276
Relation :
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000300153&lng=en&tlng=en; https://doaj.org/toc/1678-8060
DOI :
10.1590/0074-02760170267
Access URL :
https://doaj.org/article/9bd06671af50451dad8407fc45126304
Accession Number :
edsdoj.9bd06671af50451dad8407fc45126304
Academic Journal
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.

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