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dc.contributor.author
Martínez Sayé, Melisa Soledad
dc.contributor.author
Fargnoli, Lucía
dc.contributor.author
Reigada, Chantal
dc.contributor.author
Labadie, Guillermo Roberto
dc.contributor.author
Pereira, Claudio Alejandro
dc.date.available
2018-06-04T20:00:26Z
dc.date.issued
2017-08
dc.identifier.citation
Martínez Sayé, Melisa Soledad; Fargnoli, Lucía; Reigada, Chantal; Labadie, Guillermo Roberto; Pereira, Claudio Alejandro; Evaluation of proline analogs as trypanocidal agents through the inhibition of a Trypanosoma cruzi proline transporter; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1861; 11; 8-2017; 2913-2921
dc.identifier.issn
0304-4165
dc.identifier.uri
http://hdl.handle.net/11336/47213
dc.description.abstract
Background: Trypanosoma cruzi, the etiological agent of Chagas disease, uses proline as its main carbon source, essential for parasite growth and stage differentiation in epimastigotes and amastigotes. Since proline is involved in many essential biological processes in T. cruzi, its transport and metabolism are interesting drug targets. Methods: Four synthetic proline analogues (ITP-1B/1C/1D/1G) were evaluated as inhibitors of proline transport mediated through the T. cruzi proline permease TcAAAP069. The trypanocidal activity of the compounds was also assessed. Results: The compounds ITP-1B and ITP-1G inhibited proline transport mediated through TcAAAP069 permease in a dose-dependent manner. The analogues ITP-1B, -1D and -1G had trypanocidal effect on T. cruzi epimastigotes with IC50 values between 30 and 40μM. However, only ITP-1G trypanocidal activity was related with its inhibitory effect on TcAAAP069 proline transporter. Furthermore, this analogue strongly inhibited the parasite stage differentiation from epimastigote to metacyclic trypomastigote. Finally, compounds ITP-1B and ITP-1G were also able to inhibit the transport mediated by other permeases from the same amino acid permeases family, TcAAAP. Conclusions: It is possible to design synthetic amino acid analogues with trypanocidal activity. The compound ITP-1G is an interesting starting point for new trypanocidal drug design which is also an inhibitor of transport of amino acids and polyamines mediated by permeases from the TcAAAP family, such as proline transporter TcAAAP069 among others. General significance: The Trypanosoma cruzi amino acid transporter family TcAAAP constitutes a multiple and promising therapeutic target for the development of new treatments against Chagas disease.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Amino Acid Transport
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Proline Analogues
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Transport Inhibition
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Trypanocidal Effect
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Trypanosoma Cruzi
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Evaluation of proline analogs as trypanocidal agents through the inhibition of a Trypanosoma cruzi proline transporter
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-04T17:12:43Z
dc.journal.volume
1861
dc.journal.number
11
dc.journal.pagination
2913-2921
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Martínez Sayé, Melisa Soledad. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Fargnoli, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
dc.description.fil
Fil: Reigada, Chantal. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Labadie, Guillermo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Química Organica; Argentina
dc.description.fil
Fil: Pereira, Claudio Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Biochimica et Biophysica Acta- General Subjects
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.bbagen.2017.08.015
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0304416517302714


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