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1 October 2008 Natural Sesquiterpene Lactones are Active Against Leishmania mexicana
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In this paper, the effects of 3 natural sesquiterpene lactones, i.e., helenalin (Hln), mexicanin (Mxc), and dehydroleucodine (DhL), were evaluated using cultured Leishmania mexicana promastigotes. It was observed that the compounds inhibited the in vitro growth of the parasites at relatively low concentrations. The effect was rapid and irreversible with an estimated IC50 of 2–4 μM, while all the lactones were more effective than ketoconazole. Moreover, these compounds exhibited low cytotoxicity for mammalian cells. Hln induced strong vacuolization of the parasite cytoplasm, although pericellular microtubules were preserved. The 3 lactones induced DNA fragmentation as judged by the high labeling with the fluorescent TUNEL method, which was confirmed by electrophoresis on agarose gels. The ability of the parasites to invade Vero cells was also decreased by exposure to low concentrations of the compounds. We conclude that these compounds can affect the parasite's life cycle, possibly through multiple mechanisms. Identification of the molecular targets of these natural products and their effects on amastigotes should be determined to evaluate the possible therapeutic use of the compounds against leishmaniasis.

Patricia A. Barrera, Verónica Jimenez-Ortiz, Carlos Tonn, Oscar Giordano, Norbel Galanti, and Miguel A. Sosa "Natural Sesquiterpene Lactones are Active Against Leishmania mexicana," Journal of Parasitology 94(5), (1 October 2008).
Received: 8 October 2007; Accepted: 1 January 2008; Published: 1 October 2008

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