Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study

Detalhes bibliográficos
Autor(a) principal: Ferreira, Daiane Dias
Data de Publicação: 2018
Outros Autores: Mesquita, Juliana Tonini, Silva, Thais Alves da Costa, Romanelli, Maiara Maria, Batista, Denise da Gama Jaen, Silva, Cristiane França da, Gama, Aline Nefertiti Silva da, Neves, Bruno Junior, Melo Filho, Cleber Camilo, Soeiro, Maria de Nazare C., Andrade, Carolina Horta, Tempone, Andre Gustavo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/40483
Resumo: Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.
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spelling Ferreira, Daiane DiasMesquita, Juliana ToniniSilva, Thais Alves da CostaRomanelli, Maiara MariaBatista, Denise da Gama JaenSilva, Cristiane França daGama, Aline Nefertiti Silva daNeves, Bruno JuniorMelo Filho, Cleber CamiloSoeiro, Maria de Nazare C.Andrade, Carolina HortaTempone, Andre Gustavo2020-03-24T17:28:44Z2020-03-24T17:28:44Z2018FERREIRA, Daiane Dias et al. Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study. Journal of Venomous Animals and Toxins including Tropical Disease, v. 24, n. 30, p. 1-12, 2018.1678-9199https://www.arca.fiocruz.br/handle/icict/4048310.1186/s40409-018-0165-8engBMCDoença de ChagasTrypanosoma cruziDrogaTratamentoSertralinaRedefinição de drogasReposicionamento de drogasChagas DiseaseTrypanosoma cruziDrugTreatmentSertralineDrug repurposingDrug repositioningEfficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Goiânia, GO, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Goiânia, GO, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.Background: Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. Methods: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 μM, and activity against bloodstream trypomastigotes, with IC50 of 14 μM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. Conclusions: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.info: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/40483/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMariaNCSoeiro)DeniseGJBatista_etal_IOC_2018.pdfMariaNCSoeiro)DeniseGJBatista_etal_IOC_2018.pdfapplication/pdf1161478https://www.arca.fiocruz.br/bitstream/icict/40483/2/MariaNCSoeiro%29DeniseGJBatista_etal_IOC_2018.pdf5178ef924fcde2917d3d0a6b966194e0MD52TEXTMariaNCSoeiro)DeniseGJBatista_etal_IOC_2018.pdf.txtMariaNCSoeiro)DeniseGJBatista_etal_IOC_2018.pdf.txtExtracted texttext/plain57517https://www.arca.fiocruz.br/bitstream/icict/40483/3/MariaNCSoeiro%29DeniseGJBatista_etal_IOC_2018.pdf.txta5cf65f7cc6bf9487b46c08d64b47ccfMD53icict/404832020-03-25 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dc.title.pt_BR.fl_str_mv Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
title Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
spellingShingle Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
Ferreira, Daiane Dias
Doença de Chagas
Trypanosoma cruzi
Droga
Tratamento
Sertralina
Redefinição de drogas
Reposicionamento de drogas
Chagas Disease
Trypanosoma cruzi
Drug
Treatment
Sertraline
Drug repurposing
Drug repositioning
title_short Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
title_full Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
title_fullStr Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
title_full_unstemmed Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
title_sort Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
author Ferreira, Daiane Dias
author_facet Ferreira, Daiane Dias
Mesquita, Juliana Tonini
Silva, Thais Alves da Costa
Romanelli, Maiara Maria
Batista, Denise da Gama Jaen
Silva, Cristiane França da
Gama, Aline Nefertiti Silva da
Neves, Bruno Junior
Melo Filho, Cleber Camilo
Soeiro, Maria de Nazare C.
Andrade, Carolina Horta
Tempone, Andre Gustavo
author_role author
author2 Mesquita, Juliana Tonini
Silva, Thais Alves da Costa
Romanelli, Maiara Maria
Batista, Denise da Gama Jaen
Silva, Cristiane França da
Gama, Aline Nefertiti Silva da
Neves, Bruno Junior
Melo Filho, Cleber Camilo
Soeiro, Maria de Nazare C.
Andrade, Carolina Horta
Tempone, Andre Gustavo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ferreira, Daiane Dias
Mesquita, Juliana Tonini
Silva, Thais Alves da Costa
Romanelli, Maiara Maria
Batista, Denise da Gama Jaen
Silva, Cristiane França da
Gama, Aline Nefertiti Silva da
Neves, Bruno Junior
Melo Filho, Cleber Camilo
Soeiro, Maria de Nazare C.
Andrade, Carolina Horta
Tempone, Andre Gustavo
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
Trypanosoma cruzi
Droga
Tratamento
Sertralina
Redefinição de drogas
Reposicionamento de drogas
topic Doença de Chagas
Trypanosoma cruzi
Droga
Tratamento
Sertralina
Redefinição de drogas
Reposicionamento de drogas
Chagas Disease
Trypanosoma cruzi
Drug
Treatment
Sertraline
Drug repurposing
Drug repositioning
dc.subject.en.pt_BR.fl_str_mv Chagas Disease
Trypanosoma cruzi
Drug
Treatment
Sertraline
Drug repurposing
Drug repositioning
description Instituto Adolfo Lutz. Centro de Parasitologia e Micologia. São Paulo, SP, Brasil.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2020-03-24T17:28:44Z
dc.date.available.fl_str_mv 2020-03-24T17:28:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv FERREIRA, Daiane Dias et al. Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study. Journal of Venomous Animals and Toxins including Tropical Disease, v. 24, n. 30, p. 1-12, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/40483
dc.identifier.issn.pt_BR.fl_str_mv 1678-9199
dc.identifier.doi.none.fl_str_mv 10.1186/s40409-018-0165-8
identifier_str_mv FERREIRA, Daiane Dias et al. Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study. Journal of Venomous Animals and Toxins including Tropical Disease, v. 24, n. 30, p. 1-12, 2018.
1678-9199
10.1186/s40409-018-0165-8
url https://www.arca.fiocruz.br/handle/icict/40483
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 BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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