title: Study of 5-nitroindazoles' anti-Trypanosoma cruzi mode of action: electrochemical behaviour and ESR spectroscopic studies.
abstract: New indazole derivatives have been developed to know about structural requirements for adequate anti-Trypanosoma cruzi activity. In relation to position 1 of indazole ring, we have observed that a butylaminopentyl substituent (14) affords good activity, but N-oxidation of omega-tertiary amino moiety yields completely inactive compounds (17, 18); the substituent at position 3 of indazole ring affects drastically the in vitro activity, 3-OH derivative 13 being completely inactive. On the other hand, since compound 22, denitro-analogue of active compound 4, does not show activity, the 5-nitro substituent of indazole ring seems to be essential. Intramolecular cyclization of side chain at position 1 also affords inactive compounds (19, 20). The electrochemical studies showed that the trypanocidal 5-nitroindazole derivatives yielded nitro-anion radical via one-electron process at physiological pH. This electrochemical behaviour occurs in the parasite according to ESR experiment with the T. cruzi microsomal fraction showing that 5-nitroindazole derivatives suffer bio-reduction without reactive oxygen species generation.
authors.affiliation: Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gerpe
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aguirre
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kemmerling
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Piro
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Claudio
authors.initials: C
authors.lastname: Olea-Azar
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto