title: A proteomic analysis of the mechanism of action of naphthoimidazoles in Trypanosoma cruzi epimastigotes in vitro.
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.
authors.affiliation: Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil.
authors.forename: Rubem F S
authors.initials: RF
authors.lastname: Menna-Barreto
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Beghini
authors.forename: André T S
authors.initials: AT
authors.lastname: Ferreira
authors.forename: Antônio V
authors.initials: AV
authors.lastname: Pinto
authors.forename: Solange L
authors.initials: SL
authors.lastname: De Castro
authors.forename: Jonas
authors.initials: J
authors.lastname: Perales
mesh_terms: 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
chemical_list: D007093:Imidazoles; D009285:Naphthoquinones; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; C508726:naphthoimidazole N1