Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11995
Title: Epoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
Authors: Silva, Franklin Souza
Bourguignon, Saulo Cabral
Pereira, Bernardo Acácio Santini
Côrtes, Luzia Monteiro de Castro
Oliveira, Luiz Filipe Gonçalves de
Pons, Andrea Henriques
Finkelstein, Lea Cysne
Ferreira, Vitor Francisco
Carneiro, Paula Fernandes
Pinho, Rosa Teixeira
Caffarena, Ernesto Raul
Alves, Carlos Roberto
Affilliation: Fundação 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.
Abstract: 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.
Keywords: Leishmania amazonensis
Inhibits Serine Proteinase
Epoxy- -Lapachone
DeCS: Leishmania
Inibidores de Serino Proteinase
Serina Proteases
Issue Date: 2015
Publisher: American Society for Microbiology
Citation: 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.
DOI: 10.1128/AAC.04742-14
ISSN: 1098-6596
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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