Artículo de revista
In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones
Fecha
2004-09-15Registro en:
BIOORGANIC & MEDICINAL CHEMISTRY 12 (18): 4885-4893
0968-0896
Autor
Aguirre, G.
Boiani, Lucía
Cerecetto, Hugo
Fernández, M.
González, M.
Denicola, Ana
Otero, L.
Gambino, Dinorah
Rigol Olsen, Carolina
Olea Azar, Claudio
Faúndez Cáceres, Mario Antonio
Institución
Resumen
The in vitro growth inhibition activity of new thiosemicarbazone derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, are described. The designed compounds combine in the same molecule the thiosemicarbazone function, recently described as a potent cruzain-inhibitor moiety, and the recognised 5-nitrofuryl group, an oxidative stress promoter. Some of the derivatives were found to be very active against the cultured (epimastigote) form of the parasite, being 1.5-1.7-fold more active than the reference compound, Nifurtimox. Free radicals production was detected when the compounds were incubated in presence of mammalian-liver microsomes. The thiosemicarbazones' capacity to act as pharmacophore in the cruzain inhibition process was theoretically analysed. Frontier molecular orbital HOMO was found as an adequate descriptor in this process. Acute in vivo toxicity of two of the more active derivatives was evaluated. The results showed that these compounds are among the most potent 5-nitrofuryl derivatives tested against this parasite thus support further in vivo studies of some of these thiosemicarbazones.