Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes

Detalhes bibliográficos
Autor(a) principal: Bastos, Tanira Matutino
Data de Publicação: 2020
Outros Autores: Soares, Milena Botelho Pereira, Franco, Caio Haddad, Alcântara, Laura, Antonini, Lorenzo, Sabatino, Manuela, Mautone, Nicola, Freitas Junior, Lucio Holanda, Moraes, Carolina Borsoi, Ragno, Rino, Rotili, Dante, Schenkman, Sergio, Mai, Antonello, Moretti, Nilmar Silvio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/43563
Resumo: Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number 2018/09948-0 to NSM and 2015/22031-0 to SS]; Fundação de Amparo à Pesquisa do Estado da Bahia [grant number PNX0002/2014]; and Conselho Nacional de Desenvolvimento Científico Tecnológico [grant number 424729/2018-0 to NSM and 477143/2011-3, 445655/2014-3, and INCTV, to SS], PRIN 2016 (prot. 20152TE5PK) (to AM), AIRC 2016 (n. 19162) (to AM), and PE-2013-02355271 (to AM), PRIN 2017 (prot. 2017JL8SRX) (to RR).
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spelling Bastos, Tanira MatutinoSoares, Milena Botelho PereiraFranco, Caio HaddadAlcântara, LauraAntonini, LorenzoSabatino, ManuelaMautone, NicolaFreitas Junior, Lucio HolandaMoraes, Carolina BorsoiRagno, RinoRotili, DanteSchenkman, SergioMai, AntonelloMoretti, Nilmar Silvio2020-09-23T12:28:30Z2020-09-23T12:28:30Z2020BASTOS, Tanira Matutino et al. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. International Journal of Molecular Sciences, 2020.1661-6596https://www.arca.fiocruz.br/handle/icict/43563Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number 2018/09948-0 to NSM and 2015/22031-0 to SS]; Fundação de Amparo à Pesquisa do Estado da Bahia [grant number PNX0002/2014]; and Conselho Nacional de Desenvolvimento Científico Tecnológico [grant number 424729/2018-0 to NSM and 477143/2011-3, 445655/2014-3, and INCTV, to SS], PRIN 2016 (prot. 20152TE5PK) (to AM), AIRC 2016 (n. 19162) (to AM), and PE-2013-02355271 (to AM), PRIN 2017 (prot. 2017JL8SRX) (to RR).Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil.Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil.Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy.Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy.Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy.Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil.Universidade de São Paulo.Departamento de Microbiologia. São Paulo SP, Brasil.Sapienza University of Rome. Rome Center for Molecular Design. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy.Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Sapienza University of Rome. Drug Chemistry and Technology Department. Rome, Italy / Sapienza University of Rome. Pasteur Institute, Cenci-Bolognetti Foundation. Rome, Italy.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, a ecting more than 7 million people in the world. Benznidazole and nifurtimox are the only drugs available for treatment and in addition to causing several side e ects, are only satisfactory in the acute phase of the disease. Sirtuins are NAD+-dependent deacetylases involved in several biological processes, which have become drug target candidates in various disease settings. T. cruzi presents two sirtuins, one cytosolic (TcSir2rp1) and the latter mitochondrial (TcSir2rp3). Here, we characterized the e ects of human sirtuin inhibitors against T. cruzi sirtuins as an initial approach to develop specific parasite inhibitors. We found that, of 33 compounds tested, two inhibited TcSir2rp1 (15 and 17), while other five inhibited TcSir2rp3 (8, 12, 13, 30, and 32), indicating that specific inhibitors can be devised for each one of the enzymes. Furthermore, all inhibiting compounds prevented parasite proliferation in cultured mammalian cells. When combining the most e ective inhibitors with benznidazole at least two compounds, 17 and 32, demonstrated synergistic e ects. Altogether, these results support the importance of exploring T. cruzi sirtuins as drug targets and provide key elements to develop specific inhibitors for these enzymes as potential targets for Chagas disease treatmentengMDPITrypanosoma cruziInibidoresDesacetilaçãoTrypanosoma cruziSirtuin inhibitorsDeacetylationIdentification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/43563/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALBastos, Tanira Matutino. Identiification....pdfBastos, Tanira Matutino. 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dc.title.pt_BR.fl_str_mv Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
title Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
spellingShingle Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
Bastos, Tanira Matutino
Trypanosoma cruzi
Inibidores
Desacetilação
Trypanosoma cruzi
Sirtuin inhibitors
Deacetylation
title_short Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
title_full Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
title_fullStr Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
title_full_unstemmed Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
title_sort Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes
author Bastos, Tanira Matutino
author_facet Bastos, Tanira Matutino
Soares, Milena Botelho Pereira
Franco, Caio Haddad
Alcântara, Laura
Antonini, Lorenzo
Sabatino, Manuela
Mautone, Nicola
Freitas Junior, Lucio Holanda
Moraes, Carolina Borsoi
Ragno, Rino
Rotili, Dante
Schenkman, Sergio
Mai, Antonello
Moretti, Nilmar Silvio
author_role author
author2 Soares, Milena Botelho Pereira
Franco, Caio Haddad
Alcântara, Laura
Antonini, Lorenzo
Sabatino, Manuela
Mautone, Nicola
Freitas Junior, Lucio Holanda
Moraes, Carolina Borsoi
Ragno, Rino
Rotili, Dante
Schenkman, Sergio
Mai, Antonello
Moretti, Nilmar Silvio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Bastos, Tanira Matutino
Soares, Milena Botelho Pereira
Franco, Caio Haddad
Alcântara, Laura
Antonini, Lorenzo
Sabatino, Manuela
Mautone, Nicola
Freitas Junior, Lucio Holanda
Moraes, Carolina Borsoi
Ragno, Rino
Rotili, Dante
Schenkman, Sergio
Mai, Antonello
Moretti, Nilmar Silvio
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Inibidores
Desacetilação
topic Trypanosoma cruzi
Inibidores
Desacetilação
Trypanosoma cruzi
Sirtuin inhibitors
Deacetylation
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Sirtuin inhibitors
Deacetylation
description Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number 2018/09948-0 to NSM and 2015/22031-0 to SS]; Fundação de Amparo à Pesquisa do Estado da Bahia [grant number PNX0002/2014]; and Conselho Nacional de Desenvolvimento Científico Tecnológico [grant number 424729/2018-0 to NSM and 477143/2011-3, 445655/2014-3, and INCTV, to SS], PRIN 2016 (prot. 20152TE5PK) (to AM), AIRC 2016 (n. 19162) (to AM), and PE-2013-02355271 (to AM), PRIN 2017 (prot. 2017JL8SRX) (to RR).
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-09-23T12:28:30Z
dc.date.available.fl_str_mv 2020-09-23T12:28:30Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv BASTOS, Tanira Matutino et al. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. International Journal of Molecular Sciences, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/43563
dc.identifier.issn.pt_BR.fl_str_mv 1661-6596
identifier_str_mv BASTOS, Tanira Matutino et al. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. International Journal of Molecular Sciences, 2020.
1661-6596
url https://www.arca.fiocruz.br/handle/icict/43563
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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