The inhibition of some glutamate metabolic pathways could lead to diminished parasite survival. In this study, the effects of L-methionine sulfoximine (MS), DL-methionine sulfone (MSO), and DL-methionine sulfoxide (MSE), three glutamate analogs, on several biological processes were evaluated. We found that these analogs inhibited the growth of epimastigotes cells and showed a synergistic effect with stress conditions such as temperature, nutritional starvation, and oxidative stress. The specific activity for the reductive amination of α-ketoglutaric acid, catalyzed by the NADP+-linked glutamate dehydrogenase, showed an increase in the NADP+ levels, when MS, MSE, and MSO were added. It suggests an eventual conversion of the compounds tested by the T. cruzi cells. The fact that trypomastigote bursting was not significantly inhibited when infected cells were treated with these compounds, remarks the existence of relevant metabolic differences among the different life-cycle stages. It must be considered when proposing a new therapeutic drug. 1. Introduction Chagas’ disease, also known as American trypanosomiasis, is a parasitic illness caused by the hemoflagellate Trypanosoma cruzi, which is transmitted to humans by blood-sucking triatomine vectors. The parasite is prevalent in South and Central America and infects 12–15 million people in the region, with approximately 40,000 new cases per year, and approximately 12,500 deaths per year due to cardiac disease (WHO, http://www.who.int/tdr/). In addition, more than 100,000 chronically infected individuals currently reside in the United States, Canada, and Europe due to migration from endemic countries [1]. At present, no clinically approved drug exists for the satisfactory treatment of chronic stage of the infection. Benznidazole and nifurtimox are the only available drugs prescribed for T. cruzi and are 60–80% effective in the treatment of acute infection, but the use of these drugs to treat the chronic phase remains controversial due to their low effectiveness and high toxicity. As a consequence of the adverse reactions, oral treatments frequently have to be discontinued [2]. The limitations of existing therapies encourage the search for alternative new drugs for both the acute and chronic treatment of Chagas’ disease. T. cruzi has a complex life cycle, alternating between the insect vector and the mammalian vertebrate host, which may include humans. The parasite presents different stages during the cycle: epimastigotes (replicative and noninfective forms in the insect vector), bloodstream and metacyclic
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