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

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dc.citation.titleFrontiers in Chemistryes
dc.citation.volume8es
dc.creatorFargnoli, Lucía
dc.creatorPanozzo Zénere, Esteban Andrés
dc.creatorPagura, Lucas
dc.creatorBarisón, María Julia
dc.creatorCricco, Julia Alejandra
dc.creatorSilber, Ariel M.
dc.creatorLabadie, Guillermo Roberto
dc.date.accessioned2021-04-20T21:55:10Z
dc.date.available2021-04-20T21:55:10Z
dc.date.issued2020-08-25
dc.descriptionL-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.es
dc.descriptionPara citar este articulo: Fargnoli L, Panozzo-Zénere EA, Pagura L, Barisón MJ, Cricco JA, Silber AM and Labadie GR (2020) Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development. Front. Chem. 8:696. doi: 10.3389/fchem.2020.00696
dc.description.filFil: Fargnoli, Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.es
dc.description.filFil: Panozzo Zénere, Esteban Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.es
dc.description.filFil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Barisón, María Julia. Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. Laboratory of Biochemistry of Tryps (LaBTryps); Brazil.es
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.es
dc.description.filFil: Silber, Ariel M. Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. Laboratory of Biochemistry of Tryps (LaBTryps); Brazil.es
dc.description.filFil: Labadie, Guillermo Roberto. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR -CONICET); Argentina.es
dc.description.filFil: Labadie, Guillermo Roberto. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica; Argentina.es
dc.description.sponsorshipUniversidad Nacional de Rosario (UNR): Bio503es
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT- 2017-2096es
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo: grant 2016/06034-2es
dc.description.sponsorshipConselho Nacional de Pesquisas Científicas e Tecnológicas (CNPq): grants 404769/2018-7 and 308351/2013-4es
dc.description.sponsorshipUK Research and Innovation via the Global Challenges Research Fund under grant agreement A Global Network for Neglected Tropical Diseases grant number MR/P027989/1es
dc.formatapplication/pdf
dc.format.extent1-15es
dc.identifier.issn2296-2646es
dc.identifier.urihttp://hdl.handle.net/2133/20528
dc.language.isoenges
dc.publisherFrontiers Mediaes
dc.relation.publisherversionhttps://doi.org/10.3389/fchem.2020.00696es
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fchem.2020.00696/fulles
dc.rightsopenAccesses
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.holderFargnoli, Lucíaes
dc.rights.holderPanozzo Zénere, Esteban Andréses
dc.rights.holderPagura, Lucases
dc.rights.holderBarisón, María Juliaes
dc.rights.holderCricco, Julia Alejandraes
dc.rights.holderSilber, Ariel M.es
dc.rights.holderLabadie, Guillermo Robertoes
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectChagas Diseasees
dc.subjectProline Uptakees
dc.subjectTrypanosoma cruzi Epimastigoteses
dc.subjectCytotoxicityes
dc.subjectTarget Validationes
dc.titleTargeting L-Proline uptake as new strategy for anti-chagas drug developmentes
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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