Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: Lechuga, Guilherme Curty
Data de Publicação: 2016
Outros Autores: Borges, Júlio Cesar, Calvet, Claudia Magalhães, Araújo, Humberto Pinheiro de, Zuma, Aline Araujo, Nascimento, Samara Braga do, Motta, Maria Cristina Machado, Bernardino, Alice Maria Rolim, Pereira, Mirian Claudia de Souza, Bourguignon, Saulo Cabral
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/16534
Resumo: Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. a Laboratório de Interação Celular e Molecular. Niterói, RJ, Brasil.
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spelling Lechuga, Guilherme CurtyBorges, Júlio CesarCalvet, Claudia MagalhãesAraújo, Humberto Pinheiro deZuma, Aline AraujoNascimento, Samara Braga doMotta, Maria Cristina MachadoBernardino, Alice Maria RolimPereira, Mirian Claudia de SouzaBourguignon, Saulo Cabral2016-12-15T10:45:34Z2016-12-15T10:45:34Z2016LECHUGA, Guilherme Curty; et al. Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi. International Journal for Parasitology: Drugs and Drug Resistance, v.6, p.154-164, 2016.2211-3207https://www.arca.fiocruz.br/handle/icict/1653410.1016/j.ijpddr.2016.07.001engElsevierDoença de ChagasQuimioterapiaTrypanosoma cruziHemeQuinolinaQuinolineHemeTrypanosoma cruziChemotherapyChagas DiseaseInteractions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal Fluminense. Departamento de Biologia Celular e Molecular. a Laboratório de Interação Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Departamento de Química Organica. Niterói, RJ, Brasil / Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro. Nilópolis, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Imunologia. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. a Laboratório de Interação Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil.Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro. Nilópolis, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. a Laboratório de Interação Celular e Molecular. Niterói, RJ, Brasil.Chagas disease is a neglected tropical disease caused by the flagellated protozoan Trypanosoma cruzi. The current drugs used to treat this disease have limited efficacy and produce severe side effects. Quinolines, nitrogen heterocycle compounds that form complexes with heme, have a broad spectrum of antiprotozoal activity and are a promising class of new compounds for Chagas disease chemotherapy. In this study, we evaluated the activity of a series of 4-arylaminoquinoline-3-carbonitrile derivatives against all forms of Trypanosoma cruzi in vitro. Compound 1g showed promising activity against epimastigote forms when combined with hemin (IC50<1 μM), with better performance than benznidazole, the reference drug. This compound also inhibited the viability of trypomastigotes and intracellular amastigotes. The potency of 1g in combination with heme was enhanced against epimastigotes and trypomastigotes, suggesting a similar mechanism of action that occurs in Plasmodium spp. The addition of hemin to the culture medium increased trypanocidal activity of analog 1g without changing the cytotoxicity of the host cell, reaching an IC50 of 11.7 μM for trypomastigotes. The mechanism of action was demonstrated by the interaction of compound 1g with hemin in solution and prevention of heme peroxidation. Compound 1g and heme treatment induced alterations of the mitochondrion-kinetoplast complex in epimastigotes and trypomastigotes and also, accumulation of electron-dense deposits in amastigotes as visualized by transmission electron microscopy. The trypanocidal activity of 4-aminoquinolines and the elucidation of the mechanism involving interaction with heme is a neglected field of research, given the parasite's lack of heme biosynthetic pathway and the importance of this cofactor for parasite survival and growth. The results of this study can improve and guide rational drug development and combination treatment strategies.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/16534/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALmiriam_pereira_etal_IOC_2016.pdfmiriam_pereira_etal_IOC_2016.pdfapplication/pdf3709212https://www.arca.fiocruz.br/bitstream/icict/16534/2/miriam_pereira_etal_IOC_2016.pdf389d7125cf36328fd2a8cdabe7ab053fMD52TEXTmiriam_pereira_etal_IOC_2016.pdf.txtmiriam_pereira_etal_IOC_2016.pdf.txtExtracted texttext/plain61032https://www.arca.fiocruz.br/bitstream/icict/16534/3/miriam_pereira_etal_IOC_2016.pdf.txt86010b04a00723b31800f2d8dd72daa6MD53icict/165342022-06-24 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dc.title.pt_BR.fl_str_mv Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
title Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
spellingShingle Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
Lechuga, Guilherme Curty
Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Heme
Quinolina
Quinoline
Heme
Trypanosoma cruzi
Chemotherapy
Chagas Disease
title_short Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
title_full Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
title_fullStr Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
title_full_unstemmed Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
title_sort Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi
author Lechuga, Guilherme Curty
author_facet Lechuga, Guilherme Curty
Borges, Júlio Cesar
Calvet, Claudia Magalhães
Araújo, Humberto Pinheiro de
Zuma, Aline Araujo
Nascimento, Samara Braga do
Motta, Maria Cristina Machado
Bernardino, Alice Maria Rolim
Pereira, Mirian Claudia de Souza
Bourguignon, Saulo Cabral
author_role author
author2 Borges, Júlio Cesar
Calvet, Claudia Magalhães
Araújo, Humberto Pinheiro de
Zuma, Aline Araujo
Nascimento, Samara Braga do
Motta, Maria Cristina Machado
Bernardino, Alice Maria Rolim
Pereira, Mirian Claudia de Souza
Bourguignon, Saulo Cabral
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Lechuga, Guilherme Curty
Borges, Júlio Cesar
Calvet, Claudia Magalhães
Araújo, Humberto Pinheiro de
Zuma, Aline Araujo
Nascimento, Samara Braga do
Motta, Maria Cristina Machado
Bernardino, Alice Maria Rolim
Pereira, Mirian Claudia de Souza
Bourguignon, Saulo Cabral
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Heme
Quinolina
topic Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Heme
Quinolina
Quinoline
Heme
Trypanosoma cruzi
Chemotherapy
Chagas Disease
dc.subject.en.pt_BR.fl_str_mv Quinoline
Heme
Trypanosoma cruzi
Chemotherapy
Chagas Disease
description Universidade Federal Fluminense. Departamento de Biologia Celular e Molecular. a Laboratório de Interação Celular e Molecular. Niterói, RJ, Brasil.
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-12-15T10:45:34Z
dc.date.available.fl_str_mv 2016-12-15T10:45:34Z
dc.date.issued.fl_str_mv 2016
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 LECHUGA, Guilherme Curty; et al. Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi. International Journal for Parasitology: Drugs and Drug Resistance, v.6, p.154-164, 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/16534
dc.identifier.issn.pt_BR.fl_str_mv 2211-3207
dc.identifier.doi.none.fl_str_mv 10.1016/j.ijpddr.2016.07.001
identifier_str_mv LECHUGA, Guilherme Curty; et al. Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi. International Journal for Parasitology: Drugs and Drug Resistance, v.6, p.154-164, 2016.
2211-3207
10.1016/j.ijpddr.2016.07.001
url https://www.arca.fiocruz.br/handle/icict/16534
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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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