The trypanocidal effect of sesquiterpene lactones helenalin and mexicanin on cultured epimastigotes

VERÓNICA JIMENEZ-ORTIZ; SILVIA D. BRENGIO; OSCAR GIORDANO; CARLOS TONN; MATÍAS SANCHEZ; MARIO H. BURGOS; MIGUEL A. SOSA

JOURNAL OF PARASITOLOGY

Allen Press

Año: 2005 vol. 91 p. 170 - 174

0022-3395

Sesquiterpene lactones constitute a large group of biologically active compounds obtained from plants. The lactones mexicanin and helenalin, were recently reported as active against the infective form of Trypanosoma cruzi. In this work, we studied the effects of these compounds on the growth and viability of the non-infective epimatigote, to compare the sensitivity of the two stages rypomastigotes and to characterize their actions. Both compounds were cytotoxic to the parasites, with helenalin (IC50  1.9 ± 0.08 mM) more potent than mexicanin (IC50 3.8 ± 0.19 mM) and the typanocidal drug benznidazole (IC50 8.6 ± 2.5 mM). The results demonstrated that epimatigotes are less sensitive than trypomastigotes to the compounds. The trypanocidal effect of these lactones, irreversible after 12 hr exposure, was not reversed by the reducing agents dithiotreitol or b-mercaptoethanol. Ultrastructurally, we observed cytoplasmic vacuolization and nuclear disorganization. Although concentrations between 0.5-1.5 mM of the drugs were not lethal to the parasites, epimastigotes became thinner and their nuclei became more picnotic after exposure. We conclude that mexicanin and helenalin are deleterious for T.cruzi epimatigotes, and that their mechanism of action is different from that of the related lactone, dehydroleucodine.