Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Recently it has been demonstrated that MCPs, methylcarboxypeptidases that belong to the M32 peptidase family, are present in the cytosol of T. cruzi. Previously it was thought that these enzymes only existed in bacteria and prokaryotes. T. cruzi has two MCPs: TcMCP-1 and TcMCP-2. The former is found in all stages of the parasite, while TcMCP-2 only exists in epimastigotes and trypomastigotes. Because this enzyme does not exist in humans, its inhibition could represent an effective therapy against T. cruzi.42,43 In the last 3 years there have been many studies of drugs against T. cruzi, among those who have had good compliance both in vitro and or in animal experiments we can mentionate: fexinidazole,44 vinylsulfone,27 glycosyl disulfider,45 fenarimol and analogs,46 novel quinoxaline,47 novel 3-nitro-1- (1-1,2,4,treazole),48 pentamidine,49 squaramides,50 hydroxamic acid and derivatives,51 and lanthanide complexes.52 None of these drugs has been used in human infections yet.
Treatment of human infection
Treatment with NF and BNZ began in the 1970s and is based on an empirical treatment.53-55 NF is 4-([5-nitrofurfuryledene] amino) 3 methylthiomorpholine-1, 1-dioxide (Fig. 31.5).
It acts by the production of free radicals, superoxide anions, hydrogen peroxide, and electrophilic metabolites. It has been demonstrated that in addition to the metabolic action of the drug on T. cruzi, its incorporation and transport by the parasite is of great importance. There are strains with some resistance to NF that differ due to a lower intake and transportation of the drug, rather than by the amount of free radical production. T. cruzi in the presence of NF increases oxygen consumption, H2O2, and superoxide radical production (Fig. 31.6).
The drug BNZ (N-benzyl-2 nitroimidazole-1-acetamide) was introduced in human clinical use in 1978. The drug inhibits protein synthesis, originating a degradation of macromolecule biosynthesis. Reduced metabolites of BNZ in covalent unions with macromolecules interact with the DNA of the parasite.25 The drug inhibits the respiratory chain. The free radical production is lower than with NF.
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