Effects of sesquiterpene lactones on life cycle of Leishmania mexicana

BARRERA P; CARVELLI L; SARTOR T; TONN C; GIORDANO; GALANTI; JIMENEZ-ORTIZ; SOSA MA

Pinamar, Buenos Aires

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Leishmania mexicana is the etiological agent of cutaneous leishmaniasis that affects to millions of people in the world. Here, we evaluated the effect of natural compounds on parasites cultured in liquid medium. Three sesquiterpene lactones; helenalin (HLN), mexicanin (MXN) and dehydroleucodine (DhL) obtained from native plants were tested on viability, proliferation, morphology and invasive capability of L.mexicana. The lactones inhibited proliferation of the parasites at very low concentrations (0.25- 2.5 micro g/ml), being HLN and MXN more effective than DhL and than Ketokonazole (used as control). Moreover, cytotoxicity of these compounds was lesser in mammalian cells. We also observed that HLN and MXN induce apoptosis from concentrations of 1 micro g/ml as judged by DNA fractionation. Infective capability of the parasites on Vero cells was also evaluated, and observed that MXN and HLN (DhL at lesser extent) reduce significantly the number of infected cells. Ultrastructurally, HLN and MXN induce intense vacuolization in the cytoplasm. We concluded that the lactones studied are active against L. mexicana at doses no lethal for the host cells. These compounds could be used as agents against leishmania in future, although further studies about the mechanism of action should be addressed.