Relevance of Trypanothione Reductase Inhibitors on Trypanosoma cruzi Infection: A Systematic Review, Meta-Analysis, and In Silico Integrated Approach
Joint Authors
de Miranda, Aline Silva
Novaes, Rômulo Dias
Gonçalves, Reggiani Vilela
Santos Mendonça, Andréia Aparecida
Caldas, Ivo Santana
Coelho, Camila Morais
Veloso, Marcia Paranho
Teixeira, Antonio Lucio
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-10-24
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Due to the rudimentary antioxidant defenses in Trypanosoma cruzi, disruptors of redox balance are promising candidates for new antitrypanosomal drugs.
We developed an integrated model based on systematic review, meta-analyses, and molecular modeling to evaluate the effect of trypanothione reductase (TR) inhibitors in T.
cruzi infections.
Our findings indicated that the TR inhibitors analyzed were effective in reducing parasitemia and mortality due to Trypanosoma cruzi infection in animal models.
The most investigated drugs (clomipramine and thioridazine) showed no beneficial effects on the occurrence of infection-related electrocardiographic abnormalities or the affinity and density of cardiac β-adrenergic receptors.
The affinity between the tested ligands and the active site of TR was confirmed by molecular docking.
However, the molecular affinity score was unable to explain TR inhibition and T.
cruzi death in vitro or the antiparasitic potential of these drugs when tested in preclinical models of T.
cruzi infection.
The divergence of in silico, in vitro, and in vivo findings indicated that the anti-T.
cruzi effects of the analyzed drugs were not restricted to TR inhibition.
As in vivo studies on TR inhibitors are still scarce and exhibit methodological limitations, mechanistic and highly controlled studies are required to improve the quality of evidence.
American Psychological Association (APA)
Santos Mendonça, Andréia Aparecida& Coelho, Camila Morais& Veloso, Marcia Paranho& Caldas, Ivo Santana& Gonçalves, Reggiani Vilela& Teixeira, Antonio Lucio…[et al.]. 2018. Relevance of Trypanothione Reductase Inhibitors on Trypanosoma cruzi Infection: A Systematic Review, Meta-Analysis, and In Silico Integrated Approach. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-20.
https://search.emarefa.net/detail/BIM-1212298
Modern Language Association (MLA)
Santos Mendonça, Andréia Aparecida…[et al.]. Relevance of Trypanothione Reductase Inhibitors on Trypanosoma cruzi Infection: A Systematic Review, Meta-Analysis, and In Silico Integrated Approach. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-20.
https://search.emarefa.net/detail/BIM-1212298
American Medical Association (AMA)
Santos Mendonça, Andréia Aparecida& Coelho, Camila Morais& Veloso, Marcia Paranho& Caldas, Ivo Santana& Gonçalves, Reggiani Vilela& Teixeira, Antonio Lucio…[et al.]. Relevance of Trypanothione Reductase Inhibitors on Trypanosoma cruzi Infection: A Systematic Review, Meta-Analysis, and In Silico Integrated Approach. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-20.
https://search.emarefa.net/detail/BIM-1212298
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212298