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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