The trypanocidal activity of N-allyl (NAOx) and N-propyl (NPOx) oxamates and that of the ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested on cultured epimastigotes (in vitro) and murine trypanosomiasis (in vivo) using five different T. cruzi strains. NAOx and NPOx did not penetrate intact epimastigotes and therefore we were not able to detect any trypanocidal effect with these oxamates. Whereas the ethyl esters (Et-NAOx and Et-NPOx), acting as prodrugs, exhibited in vitro and in vivo trypanocidal activity on the five tested T. cruzi strains. On the contrary, when Nifurtimox and Benznidazole used as reference drugs were tested, we found that only three of the five tested T. cruzi strains were affected, whereas the other two strains, Miguz and Compostela, were resistant to the in vitro and in vivo trypanocidal activity of these compounds.

In this investigation we studied the trypanocidal activity of the ethyl esters of N-propyl (Et-NPOX) and N-isopropyl (Et-NIPOX) oxamates on bloodstream trypomastigotes and on the clinically relevant intracellular amastigotes of Trypanosoma cruzi acute infected mice. In the infected and treated mice, the levels of parasitemia were drastically reduced between days 15 and 20 of treatment and almost to zero between days 35 and 40. We also found that Et-NPOX completely eliminated amastigote nests in the myocardium of mice infected with INC-5 or NINOA T. cruzi strain, and in skeletal muscle the reduction in the number of amastigote nests was between 60 and 80% in both strains. Also, Et-NIPOX reduced by 60-80% the number of amastigote nests in the myocardium and skeletal muscle of mice infected with these T. cruzi strains. In contrast, nifurtimox, used for comparison, produced a reduction of amastigote nests of only 20-40% in the studied tissues in both strains.

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Jatropha curcas has considerable potential for production of biodiesel and secondary metabolites with medicinal uses. Herein, J. curcas cell suspension cultures were established to study the effect of jasmonic acid (JA) elicitation on triterpene production and oxidative responses. Cell cultures grown in dark conditions reached maximum biomass accumulation at the 12th day of culture (14.3 ± 0.45 g DW L -1 ) with a specific growth rate l = 0.131 d -1 . Elicitation with JA (200 or 400 lM) on 4-days-old cell cultures caused reduction in biomass and triterpene contents. In contrast, application of 200 lM JA at the 7th day of culture triggered triterpene accumulation by three times (1180 ± 12.3 lg g -1 DW, at day 2) with respect to control, without significant changes in biomass and viability. After 2 days of elicitation, betulin increased up to 7.3-fold (from 110.6 ± 20.7 to 808.7 ± 55.4 lg g -1 DW), while betulinic acid reached the maximum amount at day 6 after elicitation (245.6 ± 3.7 to 835 ± 41.5 lg g -1 DW). Lupeol presented a moderate increase (167.9 ± 51.0-288.8 ± 7.3 lg g -1 DW) along 8 days after elicitation. In correlation with triterpene production, JA application induced oxidative responses evaluated by an increase in the H 2 O 2 levels up to three times and of malondialdehyde by 59 %. At day 4 after elicitation, catalase showed higher increase (122 %) than peroxidases (63 %) and ascorbate peroxidase (26 %). Incorporation of radioactive labels from (R,S)-[2-14 C]mevalonic acid in triterpenes and sterols confirmed its role as metabolic precursor.

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