Natural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatids

VALERIA. P. SÜLSEN; SILVIA CAZORLA; FERNANDA M. FRANK; LAURA C. LAURELLA; LILIANA V. MUSCHIETTI; CESAR A. CATALÁN; VIRGINIA S. MARTINO; EMILIO L. MALCHIODI.

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 7 p. 1 - 10

1935-2735

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 cruzi epimastigotes with 50% inhibition concentrations (IC50) values of 2.63 and 7.37 µg/ml, respectively, and less active against trypomastigotes. Psilostachyin and cumanin were also active against amastigote forms with IC50 values of 6.27 and 9.95 µg/ml, 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. The four isolated compounds also showed leishmanicidal effect on Leishmania braziliensis promastigotes; cordilin and psilostachyin having the highest leishmanicidal activity with growth inhibitions of about 80% at a concentration of 1 µg/ml. 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 both in vitro using Vero cells and in vivo, as determined using markers of hepatic damage.