A proteomic analysis of the mechanism of action of naphthoimidazoles in Trypanosoma cruzi epimastigotes in vitro

Journal of Proteomics
Rubem F S Menna-BarretoJonas Perales

Abstract

Chagas' disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America, which current treatment presents variable efficacy and serious side effects. A previous screening of naphthoquinone derivatives pointed to the naphthoimidazoles N1, N2 and N3 as the most active compounds against T. cruzi. In this study, a proteomic approach was employed to identify proteins involved in the N1, N2 and N3 trypanocidal activity. In epimastigotes, the naphthoimidazoles are involved in multiple mechanisms: (a) redox metabolism; (b) energy production; (c) ergosterol biosynthesis; (d) cytoskeleton assembly; (e) protein metabolism and biosynthesis; and (f) chaperones modulation. They induce an imbalance in crucial pathways of the parasite, leading to the loss of metabolic homeostasis and T. cruzi death.

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Citations

Jun 22, 2012·Epidemiology and Infection·E MertensF Burckhardt
May 7, 2014·BioMed Research International·Rubem Figueiredo Sadok Menna-Barreto, Solange Lisboa de Castro
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Feb 20, 2020·Memórias do Instituto Oswaldo Cruz·Cynthia M CascabulhoRubem Fs Menna-Barreto
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Jan 5, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ana Cristina S BombaçaRubem F S Menna-Barreto
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