In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N-propyl oxamates using different Trypanosoma cruzi strains

Figures & data

Figure 1 Effect of the inhibitors N-allyl and N-propyl oxamates (NAOx and NPOx) and the corresponding ethyl esters (Et-NAOx and Et-NPOx) on the activity of HADH-isozyme II in a T. cruzi V2R strain homogenate, containing also carboxyl esterases and using α-ketoisocaproate as a substrate. Similar results were obtained in the five tested T. cruzi strains. Control without inhibitor.

Figure 2 Trypanocidal effect of Benznidazole (Bz) and Nifurtimox (Nx) on cultured epimastigotes of different T. cruzi strains. Control (without Bz or Nx). Drug concentration was 0.1 mM. Final concentration of epimastigotes was 1 × 10⁶/ mL. Cell viability was determined every 10 min during 1 h, according to Barr et al. [11]. Compostela and Miguz strains were resistant to the treatment with Nx and Bz.

Figure 3 Trypanocidal effect of the ethyl esters of N-allyl oxamate (Et-NAOx) and N-propyl oxamate (Et-NPOx) on cultured epimastigotes of different T. cruzi strains using N-allyl oxamic acid (NAOx) or N-propyl oxamic acid (NPOx) as a control. Drug concentration was 0.1 mM. Final concentration of epimastigotes was 1×10⁶/ mL. Cell viability was determined every 10 min during 1 h, according to Barr et al. [11].

Figure 4 Trypanocidal effect of Benznidazole (Bz) and Nifurtimox (Nx) on mice parasitaemia induced by different T. cruzi strains. Control (without Bz or Nx). At the peak of maximum parasitaemia, a single dose of the drug (500 mg/kg) was given by the oral route and the parasitaemia was determined before and 2,4 and 6 h after treatment, according to Filardi and Brener [14]. Compostela and Miguz strains were resistant to the treatment with Nx and Bz.

Figure 5 Trypanocidal effect of the ethyl esters of N-allyl oxamate (Et-NAOx) and N-propyl oxamate (Et-NPOx) on mice parasitaemia induced by different T. cruzi strains using N-allyl oxamic acid (NAOx) or N-propyl oxamic acid (NPOx) as a control. At the peak of maximum parasitaemia, a single dose of the drug (500 mg/kg) was given by the oral route and the parasitaemia was determined before and 2, 4 and 6 h after the treatment, according to Filardi and Brener [14].

Figure 6 (A) Comparative trypanocidal effect of Benznidazole (Bz), the ethyl ester of N-propyl oxamate (Et-NPOx), Nifurtimox (Nx) and the ethyl ester of N-allyl oxamate (Et-NAOx) on cultured epimastigotes, and (B) On mice parasitaemia using five different T. cruzi strains. In vitro, the drug concentration was 0.1 mM. Time of incubation was 1 h. Data were taken from Figures 2 and 3. Whereas, in vivo, at the peak of maximum parasitaemia of each strain, a single dose of the drug (500 mg/kg) was given by the oral route and the parasitaemia was determined 6 h after drug administration. Data were taken from Figures 4 and 5. The employed T. cruzi strains were: a) Control, b) Miguz, c) Compostela, d) Parra, e) Nayarit, f) V2R.

Barr JC, Rose D, Jaines JM. Activity of lytic peptides against intracellular trypanosoma cruzi amastigotes in vitro and parasitaemia in mice. J Parasitol 1995; 81: 974–978

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Filardi LS, Brener Z. A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents. Mem Inst Oswaldo Cruz 1984; 79: 221–225

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