Targeting L-Proline uptake as new strategy for anti-chagas drug development

L-Proline is an important amino acid for the pathogenic protists belonging to Trypanosoma and Leishmania genera. In Trypanosoma cruzi, the etiological agent of Chagas disease, this amino acid is involved in fundamental biological processes such as ATP production, differentiation of the insect and...

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Autores principales:	Fargnoli, Lucía, Panozzo Zénere, Esteban Andrés, Pagura, Lucas, Barisón, María Julia, Cricco, Julia Alejandra, Silber, Ariel M., Labadie, Guillermo Roberto
Formato:	article artículo publishedVersion
Lenguaje:	Inglés
Publicado:	Frontiers Media 2021
Materias:	Chagas Disease Proline Uptake Trypanosoma cruzi Epimastigotes Cytotoxicity Target Validation
Acceso en línea:	http://hdl.handle.net/2133/20528 http://hdl.handle.net/2133/20528
Aporte de:	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario

id	I15-R121-2133-20528
record_format	dspace
institution	Universidad Nacional de Rosario
institution_str	I-15
repository_str	R-121
collection	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language	Inglés
orig_language_str_mv	eng
topic	Chagas Disease Proline Uptake Trypanosoma cruzi Epimastigotes Cytotoxicity Target Validation
spellingShingle	Chagas Disease Proline Uptake Trypanosoma cruzi Epimastigotes Cytotoxicity Target Validation Fargnoli, Lucía Panozzo Zénere, Esteban Andrés Pagura, Lucas Barisón, María Julia Cricco, Julia Alejandra Silber, Ariel M. Labadie, Guillermo Roberto Targeting L-Proline uptake as new strategy for anti-chagas drug development
topic_facet	Chagas Disease Proline Uptake Trypanosoma cruzi Epimastigotes Cytotoxicity Target Validation
description	L-Proline is an important amino acid for the pathogenic protists belonging to Trypanosoma and Leishmania genera. In Trypanosoma cruzi, the etiological agent of Chagas disease, this amino acid is involved in fundamental biological processes such as ATP production, differentiation of the insect and intracellular stages, the host cell infection and the resistance to a variety of stresses. In this study, we explore the L-Proline uptake as a chemotherapeutic target for T. cruzi. Novel inhibitors have been proposed containing the amino acid with a linker and a variable region able to block the transporter. A series of sixteen 1,2,3-triazolyl-proline derivatives have been prepared for in vitro screening against T. cruzi epimastigotes and proline uptake assays. We successfully obtained inhibitors that interfere with the amino acid internalization, which validated our design targeting the metabolite’s transport. The presented structures are one of few examples of amino acid transporter inhibitors. The unprecedent application of this strategy on the development of new chemotherapy against Chagas disease, opens a new horizon on antiparasitic drug development against parasitic diseases and other pathologies.
format	article artículo publishedVersion
author	Fargnoli, Lucía Panozzo Zénere, Esteban Andrés Pagura, Lucas Barisón, María Julia Cricco, Julia Alejandra Silber, Ariel M. Labadie, Guillermo Roberto
author_facet	Fargnoli, Lucía Panozzo Zénere, Esteban Andrés Pagura, Lucas Barisón, María Julia Cricco, Julia Alejandra Silber, Ariel M. Labadie, Guillermo Roberto
author_sort	Fargnoli, Lucía
title	Targeting L-Proline uptake as new strategy for anti-chagas drug development
title_short	Targeting L-Proline uptake as new strategy for anti-chagas drug development
title_full	Targeting L-Proline uptake as new strategy for anti-chagas drug development
title_fullStr	Targeting L-Proline uptake as new strategy for anti-chagas drug development
title_full_unstemmed	Targeting L-Proline uptake as new strategy for anti-chagas drug development
title_sort	targeting l-proline uptake as new strategy for anti-chagas drug development
publisher	Frontiers Media
publishDate	2021
url	http://hdl.handle.net/2133/20528 http://hdl.handle.net/2133/20528
work_keys_str_mv	AT fargnolilucia targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT panozzozenereestebanandres targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT paguralucas targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT barisonmariajulia targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT criccojuliaalejandra targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT silberarielm targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment AT labadieguillermoroberto targetinglprolineuptakeasnewstrategyforantichagasdrugdevelopment
bdutipo_str	Repositorios
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Targeting L-Proline uptake as new strategy for anti-chagas drug development

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