Key proteins in the polyamine-trypanothione pathway as drug targets against Trypanosoma cruzi
Author
dc.contributor.author
Maya Arango, Juan
Author
dc.contributor.author
Salas, C. O.
Author
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Aguilera Venegas, Benjamín
Author
dc.contributor.author
Diaz, M. V.
Author
dc.contributor.author
López-Muñoz, R.
Admission date
dc.date.accessioned
2019-03-15T16:06:33Z
Available date
dc.date.available
2019-03-15T16:06:33Z
Publication date
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2014
Cita de ítem
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Current Medicinal Chemistry, Volumen 21, Issue 15, 2018, Pages 1757-1771
Identifier
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1875533X
Identifier
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09298673
Identifier
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10.2174/0929867320666131119122145
Identifier
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https://repositorio.uchile.cl/handle/2250/166150
Abstract
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In trypanosomatids, redox homeostasis is centered on trypanothione (N 1,N8-bis(glutathionyl)spermidine, T(SH)2), a low molecular weight thiol that is distinctive for this taxonomic family and not present in the mammalian host. Thus, the study of the metabolism of T(SH)2 is interesting as a potential therapeutic target. In this review, we summarize the existing evidence about the metabolism of thiols in Trypanosoma cruzi, focused on those proteins that can be considered the best candidates for selective therapy. Herein, we examine the biosynthetic pathway of T(SH) 2, identifying three key points that are susceptible to attack pharmacologically: the activity of the trypanothione reductase (TR), the function of glutamate-cysteine ligase (GCL) and polyamine transport in T. cruzi. TR has been widely studied and is a good example for the development of the medicinal chemistry of antichagasic compounds. Conversely, GCL and the polyamine uptake system are high flow points in the reductive meta