IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
artículos
Título:
Natural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatids.
Autor/es:
SÜLSEN VP, CAZORLA SI, FRANK FM, LAURELLA LC, MUSCHIETTI LV, CATALÁN CA, MARTINO VS, MALCHIODI EL
Revista:
PLOS NEGLECTED TROPICAL DISEASES
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2013 p. 2494 - 2494
ISSN:
1935-2735
Resumen:
Among the natural compounds, terpenoids play an important role in the drug discovery process for tropical diseases. The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol, were isolated from A. scabra. Cumanin and cordilin were active against Trypanosoma cruziepimastigotes showing 50% inhibition concentrations (IC50) values of 12 mM and 26 mM, respectively. Moreover, these compounds are active against bloodstrean trypomastigotes, regardless of the T. cruzi strain tested. Psilostachyin and cumanin were also active against  amastigote forms with IC50 values of 21 mM and 8 mM, respectively. By contrast, daucosterol showed moderate activity on epimastigotes and trypomastigotes and was inactive against amastigote forms. We also found that cumanin and psilostachyin exhibited an additive effect in their trypanocidal activity when these two drugs were tested together. Cumanin has leishmanicidal activity with growth inhibition values greater than 80% at a concentration of 5 mg/ml (19 mM), against both L. braziliensis and L. amazonensis promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active than benznidazole, producing an 8-fold reduction in parasitemia levels during the acute phase of the infection compared with the control group, and more  importantly, a reduction in mortality with 66% of the animals surviving, in comparison with 100% mortality in the control group. Cumanin also showed nontoxic effects at the doses assayed in vivo, as determined using markers of hepatic damage.
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