Sesquiterpene lactones constitute a large group of biologically active compounds obtained from plants. The lactones, mexicanin (MXN) and helenalin (HLN), were reported recently 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 noninfective epimastigote, to compare the sensitivity of the 2 stages and to characterize their actions. Both compounds were cytotoxic to the parasites, with HLN (inhibitory concentration 50% [IC 50 ] 1.9 ± 0.08 μM) more potent than MXN (IC 50 3.8 ± 0.19 μM) and the typanocidal drug, benznidazole (IC 50 8.6 ± 2.5 μM). The results showed that epimastigotes 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 β-mercaptoethanol. Ultrastructurally, we observed cytoplasmic vacuolization and nuclear disorganization. Although concentrations between 0.5 and 1.5 μM of the drugs were not lethal to the parasites, epimastigotes became thinner and their nuclei became more pycnotic after exposure. We conclude that MXN and HLN are deleterious for T. cruzi epimastigotes and that their mechanism of action is different than that of the related lactone, dehydroleucodine.

Here,we report an inhibitory effect of a sesquiterpene lactone dehydroleucodine (DhL) on the growth of Trypanosoma cruzi in culture. At concentrations of the drug between 5 and 10 µg/ml in the medium,the parasites remained alive for at least 4 days. Higher concentrations of DhL were lethal for the parasites within a few hours. The effect of DhL is irreversible. Morphological changes induced by DhL were also observed in the parasites. The effect of DhL was blocked by the presence of reducing substrates such as glutathione or dithiothreitol, but these agents were not able to reverse the effect of DhL if added 2 days after the start of drug exposure.