A proteomic analysis of the mechanism of action of naphthoimidazoles in Trypanosoma cruzi epimastigotes in vitro.
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.
Menna-Barreto
Rubem F S
RF
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil.
Beghini
Daniela G
DG
Ferreira
André T S
AT
Pinto
Antônio V
AV
De Castro
Solange L
SL
Perales
Jonas
J
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D015536:Down-Regulation; D007093:Imidazoles / Q000627:therapeutic use*; D009285:Naphthoquinones / Q000627:therapeutic use*; D015800:Protozoan Proteins / Q000096:biosynthesis; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
D007093:Imidazoles; D009285:Naphthoquinones; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; C508726:naphthoimidazole N1