Trypanocidal activity of N-isopropyl oxamate on cultured epimastigotes and murine trypanosomiasis using different Trypanosoma cruzi strains.
The trypanocidal activity of N-isopropyl oxamate (NIPOx) and the ethyl ester of N-isopropyl oxamate (Et-NIPOx) were tested on cultured epimastigotes (in vitro) and on murine trypanosomiasis (in vivo) using five different T. cruzi strains. When benznidazole and nifurtimox, used for comparison, were tested we found that only three of these T. cruzi strains were affected, whereas the other two strains, Miguz and Compostela, were resistant to the in vitro and the in vivo trypanocidal activity of these substances. In addition, when NIPOx was tested on cultured epimastigotes and on mice parasitaemia, trypanocidal activity was not obtained on either of these T. cruzi strains. Our experiments strongly suggest that NIPOx does not penetrate intact epimastigotes due to the polarity of its carboxylate whereas Et-NIPOx, acting as a prodrug, exhibited in vitro and in vivo trypanocidal activity in the five tested T. cruzi strains.
Chena
Miguel A
MA
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas-Instituto Politécnico Nacional, Apartado Postal 4-129, Admon. 4, México City 06401, México.
Elizondo
Silvia
S
Rodríguez-Páez
Lorena
L
Nogueda
Benjamín
B
Baeza
Isabel
I
Wong
Carlos
C
D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D009243:NAD / Q000378:metabolism; D009547:Nifurtimox / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013045:Species Specificity; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000378:metabolism*; D014352:Trypanosomiasis / Q000188:drug therapy*
D004791:Enzyme Inhibitors; C109929:N-isopropyloxamate; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009243:NAD; D000429:Alcohol Oxidoreductases; C021379:D-2-hydroxyacid dehydrogenase; D009547:Nifurtimox; D010072:Oxamic Acid; C009999:benzonidazole