Resumen

PONTE-SUCRE, A. Functional analysis of trypanocidal effect of selected compounds. AVFT [online]. 2015, vol.34, n.4, pp.47-52. ISSN 0798-0264.

Human African Trypanosomiasis is a vector-borne disease, fatal if left untreated. The annual incidence of patients used to be outrageous, but it has dropped to less than 10,000 per year. This statement has been used to assert that it is not necessary to invest in the development of new drugs against sleeping sickness. However, the disease may return, increasingly aggressive. Only a small number of compounds are being analyzed in clinical settings and the survival rate of candidates is normally low; none of the candidates is actually in phase three evaluation. Previously we assessed the morphological and ultrastructural changes produced by members of families of compounds synthesized within the frame of our university consortium multicenter project, led by Professor Ulrike Holzgrabe and Gerhard Bringmann, University of Würzburg, Germany on Trypanosoma brucei. The data suggested that the endoplasmic reticulum membrane systems (for the bisquaternary bisnaphthalimide 37) and the mitochondria and kinetoplast (for the N-Arylpyridinium salt 88) might be the potential organelles targeted. Herein we have determined whether these compounds are parasitostatic or parasitocydal, act synergistically with classical trypanocydal drugs and if they affect the metabolic status of the cell. Our results suggest that 37 seems to be parasitocidal while 88 seems to be parasitostatic, but that both compounds exert a synergistic effect with pentamidine, and 37 eflornithine. We further determined 37 and 88 did not alter the parasite ADP/ATP ratio or the parasite glucose levels thus indicating that they do not alter the metabolic status of the parasite.

Palabras clave : Trypanosoma brucei; sleeping sickness; bisquaternary bisnaphthalimide; N-Arylpyridinium salt; metabolic effect; synergism.

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