TY - JOUR
T1 - Trypanocidal activity of N-isopropyl oxamate on cultured epimastigotes and murine trypanosomiasis using different Trypanosoma cruzi strains
AU - Chena, Miguel A.
AU - Elizondo, Silvia
AU - Rodríguez-Páez, Lorena
AU - Nogueda, Benjamín
AU - Baeza, Isabel
AU - Wong, Carlos
N1 - Funding Information:
This work was partially supported by research grants from the Coordinación de Estudios de Posgrado e Investigación del Instituto Politécnico Nacional (CGEPI-IPN), México. C. W., L.R.P., B.N. and I.B. are fellows of the COFAA-IPN and M.A.C. and S.E. are fellows of the PIFI-IPN.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Ethyl N-isopropyl oxamate
KW - Inhibition
KW - N-isopropyl oxamate
KW - Trypanosoma cruzi
KW - α-hydroxyacid dehydrogenase (HADH)
KW - α-hydroxyacid dehydrogenase-isozyme II
UR - http://www.scopus.com/inward/record.url?scp=18444405242&partnerID=8YFLogxK
U2 - 10.1080/14756360500047019
DO - 10.1080/14756360500047019
M3 - Artículo
SN - 1475-6366
VL - 20
SP - 189
EP - 197
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 2
ER -