Study of 5-nitroindazoles' anti-Trypanosoma cruzi mode of action: Electrochemical behaviour and ESR spectroscopic studies
Author
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Rodríguez, Jorge
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Gerpe, Alejandra
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Aguirre, Gabriela
Author
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Kemmerling Weis, Ulrike
Author
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Piro, Oscar
Author
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Arán, Vicente
Author
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Maya Arango, Juan
Author
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Olea Azar, Claudio
Author
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González, Mercedes
Author
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Cerecetto, Hugo
Admission date
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2018-12-20T15:10:06Z
Available date
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2018-12-20T15:10:06Z
Publication date
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2009
Cita de ítem
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European Journal of Medicinal Chemistry, Volumen 44, Issue 4, 2009, Pages 1545-1553
Identifier
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02235234
Identifier
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17683254
Identifier
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10.1016/j.ejmech.2008.07.018
Identifier
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https://repositorio.uchile.cl/handle/2250/158143
Abstract
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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. (C) 2008 Elsevier Masson SAS. All rights reserved.