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Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

By Miguel A Chena, Silvia Elizondo-Jiménez, Lorena Rodríguez-Páez, Benjamín Nogueda-Torres, Isabel Baeza-Ramírez and Carlos Wong-Ramírez


N-allyl (NAOx) and N-propyl (NPOx) oxamates were designed as inhibitors of alpha-hydroxyacid dehydrogenase (HADH) isozyme II from Trypanosoma cruzi. The kinetic studies showed that NAOx and NPOx were competitive inhibitors of HADH-isozyme II (Ki = 72 µM, IC50 = 0.33 mM and 70 µM, IC50 = 0.32 mM, respectively). The attachment of the allylic and propylic chains to nitrogen of the competitive inhibitor oxamate (Ki = 0.91 mM, IC50 = 4.25 mM), increased 12.6 and 13-folds respectively, the affinity for T. cruzi HADH-isozyme II. NAOx and NPOx were selective inhibitors of HADH-isozyme II, because other T. cruzi dehydrogenases were not inhibited by these substances. Since HADH-isozyme II participates in the energy metabolism of T. cruzi, a trypanocidal effect can be expected with these inhibitors. However, we were not able to detect any trypanocidal activity with these oxamates. When the corresponding ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested as a possible trypanocidal prodrugs, in comparison with nifurtimox and benznidazole, the expected trypanocidal effects were obtained

Topics: Trypanosoma cruzi, Trypanosoma cruzi alpha-hydroxyacid dehydrogenase-isozyme II inhibition, N-allyl oxamate, N-propyl oxamate, ethyl N-propyl oxamate, ethyl N-allyl oxamate, alpha-hydroxyacid dehydrogenase, Microbiology, QR1-502, Science, Q, DOAJ:Microbiology, DOAJ:Biology, DOAJ:Biology and Life Sciences, Arctic medicine. Tropical medicine, RC955-962, Special situations and conditions, RC952-1245, Internal medicine, RC31-1245, Medicine, R, DOAJ:Internal medicine, DOAJ:Medicine (General), DOAJ:Health Sciences
Publisher: Instituto Oswaldo Cruz, Ministério da Saúde
Year: 2004
DOI identifier: 10.1590/S0074-02762004000800009
OAI identifier:
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