Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1128/AAC.04742-14 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/11995 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. |
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Silva, 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 Roberto2015-10-20T11:42:09Z2015-10-20T11:42:09Z2015Silva, 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://www.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:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11995/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALfranklin_silva_etal_IOC_2015.pdffranklin_silva_etal_IOC_2015.pdfapplication/pdf1013146https://www.arca.fiocruz.br/bitstream/icict/11995/2/franklin_silva_etal_IOC_2015.pdfbe96d0796e9c134498a1da35c9fc956eMD52TEXTfranklin_silva_etal_IOC_2015.pdf.txtfranklin_silva_etal_IOC_2015.pdf.txtExtracted texttext/plain51018https://www.arca.fiocruz.br/bitstream/icict/11995/3/franklin_silva_etal_IOC_2015.pdf.txtc917fbbdfd957cdd4afcb5f1a602b2acMD53icict/119952023-09-05 10:36:25.063oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-05T13:36:25Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.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 |
| 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.contributor.author.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 |
| dc.subject.en.pt_BR.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.pt_BR.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. |
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2015 |
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2015-10-20T11:42:09Z |
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2015-10-20T11:42:09Z |
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2015 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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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. |
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https://www.arca.fiocruz.br/handle/icict/11995 |
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1098-6596 |
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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 |
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American Society for Microbiology |
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American Society for Microbiology |
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