Trypanothione reductase activity is prominent in metacyclic promastigotes and axenic amastigotes of Leishmania amazonesis. Evaluation of its potential as a therapeutic target.
The activity of trypanothione reductase in Leishmania amazonensis was evaluated and it was demonstrated that TR is expressed in the soluble fractions of infective promastigotes and amastigotes, while non-infective promastigotes expressed the enzyme at basal levels. This data allows an association of enzyme activity and the infective capacity of the parasite. We have also previously demonstrated that amidine compounds (N, N'-diphenyl-4-methoxy-benzamidine and pentamidine) were active against this parasite. Here, experiments concerning the effect of these compounds on TR activity, showed that both compounds significantly inhibited the enzyme. However, against glutathione reductase, only pentamidine showed a significant inhibitory action, suggesting an association with the toxic effects of this drug used in the clinic for the treatment of leishmaniasis.
Castro-Pinto
Denise B
DB
Department of Immunology, Oswaldo Cruz Institute, FIOCRUZ, Av. Brasil, 4365-Manguinhos CEP 21042-900, Rio de Janeiro, RJ, Brazil.
Echevarria
Aurea
A
Genestra
Marcelo S
MS
Cysne-Finkelstein
Léa
L
Leon
Leonor L
LL
D000578:Amidines / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism*; D007894:Leishmania mexicana / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000578:Amidines; D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase