Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , |
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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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 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
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 |
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https://www.arca.fiocruz.br/handle/icict/40483 |
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