Trypanocidal and Leishmanicidal activities of psilostachyin, a sesquiterpene lactone isolated from Ambrosia tenuifolia Sprengel ( Asteraceae).

VALERIA SÜLSEN, SILVIA CAZORLA, FERNANDA FRANK, CLAUDIA ANESINI, BLANCA FREIXA, ROSER VILA, SALVADOR CAÑIGUERAL, LILIANA MUSCHIETTI, VIRGINIA MARTINO

La Plata, Buenos Aires

Congreso; SILAE, XVI Congreso Italo- Latinoamericano de Etnomedicina; 2007

Sociedad Italo-Latinoamericana de Etnomedicina

Introduction: Trypanosomiasis and leishmaniasis are widespread protozoal diseases that particularly afflict the poor in Latin America, Africa, and Asia and have been neglected by the pharmaceutical industry and governments. New drugs and treatments to replace the available toxic and ineffective drugs is a real need. Aims: To isolate and identify trypanocidal and leishmanicidal compounds from Ambrosia tenuifolia. Material and Methods: The aerial parts of A. tenuifolia were extracted with dichloromethane-methanol (1:1) and this extract fractionated, by column chromatography, into 5 fractions (F1AT-F5AT). Each fraction was tested against Trypanosoma cruzi epimastigotes using the 3H-thymidine uptake technique. Psilostachyin  crystallized from fraction F4AT and was identified by IR, MS, 1H-NMR and 13C-NMR. The in vitro parasiticidal activity of psilostachyin (0.3 to 100 μg/ml) was investigated on T. cruzi epi and trypomastigotes and also on promastigotes of Leishmania mexicana. This compound (1mg/kg/day, i.p) was also tested in vivo on mice infected with T. cruzi trypomastigotes. Parasitaemia and mortality were monitored every other day. Besides, the selectivity index (SI) ratio (CC50 for murine T-lymphocytes/IC50 for protozoans) was carried out.   Results: Fraction F4AT showed the strongest trypanocidal activity against T. cruzi epimastigotes (IC50=2.49 μg/ml). IC50 values for psilostachyin on T. cruzi epimastigotes and trypomastigotes were 1.22 and 0.76 µg/ml respectively. In vivo, this compound significantly reduced the level of parasitaemia and showed 100% survival. Psilostachyin exhibited a significant leishmanicidal activity with an IC50 value of 0.02 μg/ml. The SI values were 21.8 for T. cruzi trypomastigotes and 150.0 for L. mexicana promastigotes. Conclusion: The results obtained suggest that psilostachyin could be considered a lead molecule, with slight toxicity for mammalian cells, and may be a potential candidate for novel therapeutics to treat Chagas disease and leishmaniasis. This is the first time that the antiprotozoal activity of this compound is reported.  Acknowledgments: This work was supported by PICT 2002 05-11240 (Agencia Nacional de Promoción Científica y Tecnológica), PIP 5641 (Consejo Nacional de Investigaciones Científicas y Técnicas) and UBA-SECYT B101.