Trypanocidal activity of the ethyl esters of N-propyl and N-isopropyl oxamates on intracellular amastigotes of Trypanosoma cruzi acute infected mice

Abstract

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.

Keywords::

• Trypanosoma cruzi
• prodrugs
• ethyl N-isopropyl oxamate
• ethyl N-propyl oxamate
• amastigotes

Acknowledgements

This work was partially supported by research grants from the Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-IPN), México. Four of the authors (C.W., L.R.-P., B.N., I.B.) are fellows of SNI-CONACYT and COFAA-IPN, and three of the authors (C.A.-A., F.Z.-M., J.L.T.-R.) are fellows of CONACYT and PIFI-IPN.

Declaration of interest: The authors report no conflicts of interest.