Leishmania amazonensis trypanothione reductase: evaluation of the effect of glutathione analogs on parasite growth, infectivity and enzyme activity.
Trypanothione reductase (TR) is a major enzyme in trypanosomatids. Its substrate, trypanothione is a molecule containing a tripeptide (L-glutamic acid-cysteine-glycine) coupled to a polyamine, spermidine. This redox system (TR/Trypanothione) is vital for parasite survival within the host cell and has been described as a good target for chemotherapy anti-Leishmania. The use of tripeptides analogs of glutathione would result in a decrease in trypanothione synthesis and as a consequence in TR activity. In this work, besides the enzyme potential inhibition, it also evaluated the influence of those analogs on parasite growth and on its infective capacity. The results showed a significant effect on parasite growth and infectivity and in addition TR activity was highly inhibited. These results are very promising, suggesting a potential use of those analogs as therapeutic drugs against experimental diseases caused by trypanosomatids.
Castro-Pinto
Denise Barçante
DB
Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro, Brazil.
Lima
Edson L Silva
EL
Cunha
Andrea S
AS
Genestra
Marcelo
M
De Léo
Rosa Maria
RM
Monteiro
Fabiane
F
Leon
Leonor L
LL
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D007891:Leishmania / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D008264:Macrophages / Q000469:parasitology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*
D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione