title: Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives.
abstract: With the aim of determining the actual target(s) of nitro-group bearing compounds considered as possible leads for the development of drugs against Chagas' disease, we studied in parallel nitrofurans and nitroimidazoles. We investigated nine representative compounds for the following properties: efficacy on different Trypanosoma cruzi strains, redox cyclers, inhibition of respiration, production of corresponding nitroso derivatives and intracellular thiol scavengers. Our results indicate that nifurtimox and related compounds act as redox cyclers, whereas the most active in the series, the 5-nitroimidazole megazol essentially acts as thiol scavenger particularly for trypanothione, the cofactor for trypanothione reductase, an essential enzyme in the detoxification process.
authors.affiliation: Faculty of Medicine, ICBM, Program of Molecular and Clinical Pharmacology, University of Chile, P.O. Box 70086, Santiago 7, Chile.
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Soledad
authors.initials: S
authors.lastname: Bollo
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Nuñez-Vergara
authors.forename: Juan A
authors.initials: JA
authors.lastname: Squella
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Repetto
authors.forename: Antonio
authors.initials: A
authors.lastname: Morello
authors.forename: Jacques
authors.initials: J
authors.lastname: Périé
authors.forename: Gérard
authors.initials: G
authors.lastname: Chauvière
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D009581:Nitrofurans / Q000737:chemistry / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D012119:Respiration / Q000187:drug effects; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D009581:Nitrofurans; D009593:Nitroimidazoles; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine