In vitro and in vivo antitrypanosomatid activity of 5-nitroindazoles
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. cruz...
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Published in | European journal of medicinal chemistry Vol. 44; no. 3; pp. 1034 - 1040 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Kidlington
Elsevier Masson SAS
01.03.2009
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2008.06.024 |