Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.

Detalhes bibliográficos
Autor(a) principal: Efstathiou, Antonia
Data de Publicação: 2018
Outros Autores: Meira, Cássio Santana, Gaboriaud-Kolar, Nicolas, Bastos, Tanira Matutino, Rocha, Vinícius Pinto Costa, Vougogiannopoulou, Konstantina, Skaltsounis, Alexios Leandros, Smirlis, Despina, Soares, Milena Botelho Pereira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/31279
Resumo: 7th Framework Program-PEOPLE [grant no: PIRSES-GA-2009-269301] and Dr Antonia Efstathiou was a recipient of the Post-doctoral fellowship of Excellence- SIEMENS (2016-2017) supported by the Hellenic State Scholarships Foundation IKYSIEMENS [grant no: 2016-017-0173-10398].
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spelling Efstathiou, AntoniaMeira, Cássio SantanaGaboriaud-Kolar, NicolasBastos, Tanira MatutinoRocha, Vinícius Pinto CostaVougogiannopoulou, KonstantinaSkaltsounis, Alexios LeandrosSmirlis, DespinaSoares, Milena Botelho Pereira2019-01-24T12:23:07Z2019-01-24T12:23:07Z2018EFSTATHIOU, A. et al. Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents. Virulence, v. 9, n. 1, p. 1658–1668, 2018.2150-5594https://www.arca.fiocruz.br/handle/icict/3127910.1080/21505594.2018.15322427th Framework Program-PEOPLE [grant no: PIRSES-GA-2009-269301] and Dr Antonia Efstathiou was a recipient of the Post-doctoral fellowship of Excellence- SIEMENS (2016-2017) supported by the Hellenic State Scholarships Foundation IKYSIEMENS [grant no: 2016-017-0173-10398].Hellenic Pasteur Institute. Molecular Parasitology Laboratory. Department of Microbiology. Athens, Greece.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.University of Athens. Pharmacognosy and Pharmaceutical Chemistry Laboratory. Department of Pharmacy, Panepistimiopolis Zografou. Athens, Greece.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.University of Athens. Pharmacognosy and Pharmaceutical Chemistry Laboratory. Department of Pharmacy, Panepistimiopolis Zografou. Athens, Greece.University of Athens. Pharmacognosy and Pharmaceutical Chemistry Laboratory. Department of Pharmacy, Panepistimiopolis Zografou. Athens, Greece.Hellenic Pasteur Institute. Molecular Parasitology Laboratory. Department of Microbiology. Athens, Greece.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Current treatment for combatting Chagas disease, a life-threatening illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi is inadequate, and thus the discovery of new antiparasitic compounds is of prime importance. Previous studies identified the indirubins, a class of ATP kinase inhibitors, as potent growth inhibitors of the related kinetoplastid Leishmania. Herein, we evaluated the inhibitory activity of a series of 69 indirubin analogues screened against T. cruzi trypomastigotes and intracellular amastigotes. Seven indirubins were identified as potent T. cruzi inhibitors (low μΜ, nM range). Cell death analysis of specific compounds [3'oxime-6-bromoindirubin(6-BIO) analogues 10, 11 and 17, bearing a bulky extension on the oxime moiety and one 7 substituted analogue 32], as evaluated by electron microscopy and flow cytometry, showed a different mode of action between compound 32 compared to the three 6-BIO oxime- substituted indirubins, suggesting that indirubins may kill the parasite by different mechanisms dependent on their substitution. Moreover, the efficacy of four compounds that show the most potent anti-parasitic effect in both trypomastigotes and intracellular amastigotes (10, 11, 17, 32), was evaluated in a mouse model of T. cruzi infection. Compound 11 (3'piperazine-6-BIO) displayed the best in vivo efficacy (1/6 mortality, 94.5% blood parasitaemia reduction, 12 dpi) at a dose five times reduced over the reference drug benznidazole (20 mg/kg vs100 mg/kg). We propose 3'piperazine-6-BIO as a potential lead for the development of new treatments of Chagas disease.engTaylor & FrancisIndirubinsT. cruziAntiparasitárioEficácia in vivoIndirubinsT. cruziAntiparasiticIn vivo efficacyIndirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.info: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/31279/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALEFSTATHIOU, A. Indirubin derivativeS...2018.pdfEFSTATHIOU, A. Indirubin derivativeS...2018.pdfapplication/pdf2395282https://www.arca.fiocruz.br/bitstream/icict/31279/2/EFSTATHIOU%2c%20A.%20Indirubin%20derivativeS...2018.pdf1a13182db8dadacf31b3d8d7dca19322MD52TEXTEFSTATHIOU, A. 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dc.title.pt_BR.fl_str_mv Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
title Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
spellingShingle Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
Efstathiou, Antonia
Indirubins
T. cruzi
Antiparasitário
Eficácia in vivo
Indirubins
T. cruzi
Antiparasitic
In vivo efficacy
title_short Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
title_full Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
title_fullStr Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
title_full_unstemmed Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
title_sort Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.
author Efstathiou, Antonia
author_facet Efstathiou, Antonia
Meira, Cássio Santana
Gaboriaud-Kolar, Nicolas
Bastos, Tanira Matutino
Rocha, Vinícius Pinto Costa
Vougogiannopoulou, Konstantina
Skaltsounis, Alexios Leandros
Smirlis, Despina
Soares, Milena Botelho Pereira
author_role author
author2 Meira, Cássio Santana
Gaboriaud-Kolar, Nicolas
Bastos, Tanira Matutino
Rocha, Vinícius Pinto Costa
Vougogiannopoulou, Konstantina
Skaltsounis, Alexios Leandros
Smirlis, Despina
Soares, Milena Botelho Pereira
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Efstathiou, Antonia
Meira, Cássio Santana
Gaboriaud-Kolar, Nicolas
Bastos, Tanira Matutino
Rocha, Vinícius Pinto Costa
Vougogiannopoulou, Konstantina
Skaltsounis, Alexios Leandros
Smirlis, Despina
Soares, Milena Botelho Pereira
dc.subject.other.pt_BR.fl_str_mv Indirubins
T. cruzi
Antiparasitário
Eficácia in vivo
topic Indirubins
T. cruzi
Antiparasitário
Eficácia in vivo
Indirubins
T. cruzi
Antiparasitic
In vivo efficacy
dc.subject.en.pt_BR.fl_str_mv Indirubins
T. cruzi
Antiparasitic
In vivo efficacy
description 7th Framework Program-PEOPLE [grant no: PIRSES-GA-2009-269301] and Dr Antonia Efstathiou was a recipient of the Post-doctoral fellowship of Excellence- SIEMENS (2016-2017) supported by the Hellenic State Scholarships Foundation IKYSIEMENS [grant no: 2016-017-0173-10398].
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2019-01-24T12:23:07Z
dc.date.available.fl_str_mv 2019-01-24T12:23:07Z
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 EFSTATHIOU, A. et al. Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents. Virulence, v. 9, n. 1, p. 1658–1668, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/31279
dc.identifier.issn.pt_BR.fl_str_mv 2150-5594
dc.identifier.doi.none.fl_str_mv 10.1080/21505594.2018.1532242
identifier_str_mv EFSTATHIOU, A. et al. Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents. Virulence, v. 9, n. 1, p. 1658–1668, 2018.
2150-5594
10.1080/21505594.2018.1532242
url https://www.arca.fiocruz.br/handle/icict/31279
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 Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/31279/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/31279/2/EFSTATHIOU%2c%20A.%20Indirubin%20derivativeS...2018.pdf
https://www.arca.fiocruz.br/bitstream/icict/31279/3/EFSTATHIOU%2c%20A.%20Indirubin%20derivativeS...2018.pdf.txt
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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