title: Evaluation of thiosemicarbazones and semicarbazones as potential agents anti-Trypanosoma cruzi.
abstract: Synthetic thiosemicarbazones and semicarbazones were evaluated for their Trypanosoma cruzi trypomastigotes obtained from LLC-MK2 cell cultures. In general, thiosemicarbazone derivatives were most effective and among them the 4-N-(2'-methoxy styryl)-thiosemicarbazone was chosen, to compare the in vitro effect against amastigotes of T. cruzi lodged in mouse peritoneal and human macrophages. A potent trypanocidal effect was observed that was more pronounced against parasites internalized in human macrophages. A potential target for this compound was also evaluated by measuring the nitric oxide synthase activity through NADPH consumption. A significant decrease in enzyme activity was observed. In contrast to the cytotoxic effect observed with benznidazole, no macrophage toxicity was observed for any of the compounds, indicating that their activity was specific for the parasite forms investigated.
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Renata O A
authors.initials: RO
authors.lastname: Soares
authors.forename: Aurea
authors.initials: A
authors.lastname: Echevarria
authors.forename: Myrtes S S
authors.initials: MS
authors.lastname: Bellieny
authors.forename: Rosa T
authors.initials: RT
authors.lastname: Pinho
authors.forename: Rosa M M
authors.initials: RM
authors.lastname: de Leo
authors.forename: Wellingon S
authors.initials: WS
authors.lastname: Seguins
authors.forename: Gérzia M
authors.initials: GM
authors.lastname: Machado
authors.forename: Marilene M
authors.initials: MM
authors.lastname: Canto-Cavalheiro
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy; D006801:Humans; D008264:Macrophages / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012664:Semicarbazones / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D012664:Semicarbazones; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D019001:Nitric Oxide Synthase