Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae)

Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), Cátedra de Inmunología, IDEHU (UBA-CONICET), Facultad de Farmacia y Bioquímica, UBA, Departamento de Microbiología, Facultad de Medicina, UBA, Buenos Aires, Argentina; Unitat de Farmacologia i Farmacognòsia, Facultat de Farmacia, Universitat de Barcelona, Barcelona, España

^* To whom correspondence should be addressed. Email: lmusch{at}ffyb.uba.ar.

	Abstract

Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods (¹H and ¹³CNMR, DEPT, COSY, HMQC, EI-MS and IR) these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in-vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC₅₀) values less than 2 µg/ml. Psilostachyin exerted a significant in-vitro activity against the trypomastigote forms of T. cruzi (IC₅₀= 0.76 µg/ml) and was selected for in-vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania spp. promastigotes: psilostachyin (IC₅₀ =0.12 µg/ml) and peruvin (IC₅₀ =0.39 µg/ml) exerted significant leishmanicidal activity. This is the first time that the trypanocidal and leishmanicidal activities of these compounds are reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T-lymphocytes. Although the SI of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI=33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein, suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis.