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

dc.creatorSilva, Franklin Souza
dc.creatorBourguignon, Saulo Cabral
dc.creatorPereira, Bernardo Acácio Santini
dc.creatorCôrtes, Luzia Monteiro de Castro
dc.creatorOliveira, Luiz Filipe Gonçalves de
dc.creatorPons, Andrea Henriques
dc.creatorFinkelstein, Léa Cysne
dc.creatorFerreira, Vitor Francisco
dc.creatorCarneiro, Paula Fernandes
dc.creatorPinho, Rosa Teixeira
dc.creatorCaffarena, Ernesto Raul
dc.creatorAlves, Carlos Roberto
dc.date2015-10-20T11:42:09Z
dc.date2015-10-20T11:42:09Z
dc.date2015
dc.date.accessioned2023-09-26T21:11:26Z
dc.date.available2023-09-26T21:11:26Z
dc.identifierSilva, 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.identifier1098-6596
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11995
dc.identifier10.1128/AAC.04742-14
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8870575
dc.descriptionLeishmania (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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectLeishmania amazonensis
dc.subjectInhibits Serine Proteinase
dc.subjectEpoxy- -Lapachone
dc.subjectLeishmania
dc.subjectInibidores de Serino Proteinase
dc.subjectSerina Proteases
dc.titleEpoxy- -Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite
dc.typeArticle


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