title: In vitro and in vivo antitrypanosomatid activity of 5-nitroindazoles.
abstract: Previously, we have identified a series of 5-nitroindazoles with good antiprotozoal activities, against Trypanosoma cruzi epimastigotes and Trichomonas vaginalis. Most of them have shown very low unspecific toxicity on macrophage cell lines. In the present work, we assayed these compounds on T. cruzi bloodstream trypomastigotes and Leishmania promastigotes (Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum). Derivatives 1, 2, 7 and 8 displayed remarkable trypanocidal activity (>80% lysis) equivalent to gentian violet. Derivatives 2 and 10, as Pentamidine, caused the complete lysis of promastigotes of Leishmania. An oxidative stress-mediated mechanism of action was confirmed for derivatives 1, 10 and 12 on T. cruzi epimastigotes. Supported by the in vitro activities, derivatives 1 and 2 were submitted to in vivo assays using an acute model of Chagas' disease and a short-term treatment. None of the animals treated with derivatives 1 and 2 died, unlike the untreated control and Benznidazole groups.
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Lucia
authors.initials: L
authors.lastname: Boiani
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gerpe
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
authors.forename: Susana
authors.initials: S
authors.lastname: Torres de Ortiz
authors.forename: Elva
authors.initials: E
authors.lastname: Serna
authors.forename: Ninfa
authors.initials: N
authors.lastname: Vera de Bilbao
authors.forename: Luis
authors.initials: L
authors.lastname: Sanabria
authors.forename: Gloria
authors.initials: G
authors.lastname: Yaluff
authors.forename: Héctor
authors.initials: H
authors.lastname: Nakayama
authors.forename: Antonieta
authors.initials: A
authors.lastname: Rojas de Arias
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: J Antonio
authors.initials: JA
authors.lastname: Morello
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D007191:Indazoles / Q000737:chemistry / Q000494:pharmacology*; D007891:Leishmania / Q000145:classification / Q000187:drug effects; D051379:Mice; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D007191:Indazoles; D014344:Trypanocidal Agents; C530840:5-nitroindazole