期刊
JOURNAL OF PROTEOMICS
卷 73, 期 12, 页码 2306-2315出版社
ELSEVIER
DOI: 10.1016/j.jprot.2010.07.002
关键词
Trypanosoma cruzi; Chagas' disease; beta-lapachone; Naphthoimidazoles; Mass spectrometry; Proteomics
资金
- CNPq
- FAPERJ
- PDTIS/FIOCRUZ
- FIOCRUZ
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. (C) 2010 Elsevier B.V. All rights reserved.
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