Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.

Detalles Bibliográficos
Autores: Silva, Franklin Souza, Bourguignon, Saulo Cabral, Pereira, Bernardo Acácio Santini, Côrtes, Luzia Monteiro de Castro, Oliveira, Luiz Filipe Gonçalves de, Pons, Andrea Henriques, Finkelstein, Léa Cysne, Ferreira, Vitor Francisco, Carneiro, Paula Fernandes, Pinho, Rosa Teixeira, Caffarena, Ernesto Raul, Alves, Carlos Roberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Brasil
Institución:Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:Repositório Institucional da FIOCRUZ (ARCA)
Idioma:inglés
OAI Identifier:oai:arca.fiocruz.br:icict/11995
Acceso en línea:https://arca.fiocruz.br/handle/icict/11995
Access Level:acceso abierto
Palabra clave:Leishmania amazonensis
Inhibits Serine Proteinase
Epoxy- -Lapachone
Leishmania
Inibidores de Serino Proteinase
Serina Proteases
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dc.title.none.fl_str_mv Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
title Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
spellingShingle Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
Silva, Franklin Souza
Leishmania amazonensis
Inhibits Serine Proteinase
Epoxy- -Lapachone
Leishmania
Inibidores de Serino Proteinase
Serina Proteases
title_short Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
title_full Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
title_fullStr Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
title_full_unstemmed Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
title_sort Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
dc.creator.none.fl_str_mv Silva, Franklin Souza
Bourguignon, Saulo Cabral
Pereira, Bernardo Acácio Santini
Côrtes, Luzia Monteiro de Castro
Oliveira, Luiz Filipe Gonçalves de
Pons, Andrea Henriques
Finkelstein, Léa Cysne
Ferreira, Vitor Francisco
Carneiro, Paula Fernandes
Pinho, Rosa Teixeira
Caffarena, Ernesto Raul
Alves, Carlos Roberto
author Silva, Franklin Souza
author_facet Silva, Franklin Souza
Bourguignon, Saulo Cabral
Pereira, Bernardo Acácio Santini
Côrtes, Luzia Monteiro de Castro
Oliveira, Luiz Filipe Gonçalves de
Pons, Andrea Henriques
Finkelstein, Léa Cysne
Ferreira, Vitor Francisco
Carneiro, Paula Fernandes
Pinho, Rosa Teixeira
Caffarena, Ernesto Raul
Alves, Carlos Roberto
author_role author
author2 Bourguignon, Saulo Cabral
Pereira, Bernardo Acácio Santini
Côrtes, Luzia Monteiro de Castro
Oliveira, Luiz Filipe Gonçalves de
Pons, Andrea Henriques
Finkelstein, Léa Cysne
Ferreira, Vitor Francisco
Carneiro, Paula Fernandes
Pinho, Rosa Teixeira
Caffarena, Ernesto Raul
Alves, Carlos Roberto
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.en.none.fl_str_mv Leishmania amazonensis
Inhibits Serine Proteinase
Epoxy- -Lapachone
topic Leishmania amazonensis
Inhibits Serine Proteinase
Epoxy- -Lapachone
Leishmania
Inibidores de Serino Proteinase
Serina Proteases
dc.subject.decs.none.fl_str_mv Leishmania
Inibidores de Serino Proteinase
Serina Proteases
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.accessioned.fl_str_mv 2015-10-20T11:42:09Z
dc.date.available.fl_str_mv 2015-10-20T11:42:09Z
dc.date.issued.fl_str_mv 2015
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 Silva, Franklin Souza; et al. Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite. Antimicrobial Agents and Chemotherapy, v.59, n.4, p.1910-1918, Apr. 2015.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/11995
dc.identifier.issn.none.fl_str_mv 1098-6596
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.04742-14
identifier_str_mv Silva, Franklin Souza; et al. Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite. Antimicrobial Agents and Chemotherapy, v.59, n.4, p.1910-1918, Apr. 2015.
1098-6596
10.1128/AAC.04742-14
url https://arca.fiocruz.br/handle/icict/11995
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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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spelling 2015-10-20T11:42:09Z2015-10-20T11:42:09Z2015Silva, Franklin Souza; et al. Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite. Antimicrobial Agents and Chemotherapy, v.59, n.4, p.1910-1918, Apr. 2015.1098-6596https://arca.fiocruz.br/handle/icict/1199510.1128/AAC.04742-14engAmerican Society for MicrobiologyEpoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasiteinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Pós-Graduação em Ciências e Biotecnologia. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapia, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy- -lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44mMepoxy- -lapachone (mean lesion area, 24.9 2.0mm2), compared to untreated animals (mean lesion area, 30.8 2.6mm2) or animals treated with Glucantime (mean lesion area, 28.3 1.5mm2). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy- -lapachone. Furthermore, in silico simulations indicated that epoxy- -lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy- -lapachone and, as such, may be related to the compound's effects on the parasite.Leishmania amazonensisInhibits Serine ProteinaseEpoxy- -LapachoneLeishmaniaInibidores de Serino ProteinaseSerina Proteasesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZSilva, Franklin SouzaBourguignon, Saulo CabralPereira, Bernardo Acácio SantiniCôrtes, Luzia Monteiro de CastroOliveira, Luiz Filipe Gonçalves dePons, Andrea HenriquesFinkelstein, Léa CysneFerreira, Vitor FranciscoCarneiro, Paula FernandesPinho, Rosa TeixeiraCaffarena, Ernesto RaulAlves, Carlos RobertoLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://arca.fiocruz.br/bitstreams/d5c36ffd-c462-47de-8e63-5649d716f262/download8b4c200b4e10021c5683c6ccaba07169MD51falseAnonymousREADORIGINALfranklin_silva_etal_IOC_2015.pdffranklin_silva_etal_IOC_2015.pdfapplication/pdf1013146https://arca.fiocruz.br/bitstreams/264d7ff1-d708-4ac9-8766-51579ce350a4/downloadbe96d0796e9c134498a1da35c9fc956eMD52trueAnonymousREADTEXTfranklin_silva_etal_IOC_2015.pdf.txtfranklin_silva_etal_IOC_2015.pdf.txtExtracted texttext/plain56868https://arca.fiocruz.br/bitstreams/d00d36ce-b0fd-429f-8188-d4ff4d1133cb/download2a3079ba619f8d94a7341bb40bf3a4e1MD59falseAnonymousREADTHUMBNAILfranklin_silva_etal_IOC_2015.pdf.jpgfranklin_silva_etal_IOC_2015.pdf.jpgGenerated Thumbnailimage/jpeg47343https://arca.fiocruz.br/bitstreams/8a8e948d-a934-472b-9791-9416693dcf2f/downloadb69cb3a9443a498b8456e5eb7e9a7c8dMD510falseAnonymousREADicict/119952025-12-10 15:41:33.632open.accessoai:arca.fiocruz.br:icict/11995https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-12-10T18:41:33Repositório Institucional da FIOCRUZ (ARCA) - 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