Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum

Detalhes bibliográficos
Autor(a) principal: Machado, Patrícia de A.
Data de Publicação: 2022
Outros Autores: Gomes, Pollyanna S., Carneiro, Monique P. D., Midlej, Victor, Coimbra, Elaine S., Guedes, Herbert L. de Matos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/54653
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil / Universidade Federal de Juiz de Fora. Núcleo de Pesquisas em Parasitologia. Juiz de Fora, MG, Brasil.
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spelling Machado, Patrícia de A.Gomes, Pollyanna S.Carneiro, Monique P. D.Midlej, VictorCoimbra, Elaine S.Guedes, Herbert L. de Matos2022-08-16T12:26:58Z2022-08-16T12:26:58Z2022MACHADO, Patrícia de A. et al. Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum. Pharmaceutics, v. 14, 1373, p. 1 - 21, June 2022.1999-4923https://www.arca.fiocruz.br/handle/icict/5465310.3390/ pharmaceutics14071373engMDPIProteases de serinaTPCKLeishmanioseLeishmania amazonensisLeishmania infantumSerine proteasesTPCKLeishmaniasisLeishmania amazonensisLeishmania infantumEffects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil / Universidade Federal de Juiz de Fora. Núcleo de Pesquisas em Parasitologia. Juiz de Fora, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro.Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal de Juiz de Fora. Núcleo de Pesquisas em Parasitologia. Juiz de Fora, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro.Instituto de Biofísica Carlos Chagas Filho. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Studies have previously demonstrated the importance of serine proteases in Leishmania. A well-known serine protease inhibitor, TPCK, was used in the present study to evaluate its in vitro and in vivo antileishmanial effects and determine its mechanism of action. Despite slight toxicity against mammalian cells (CC50 = 138.8 M), TPCK was selective for the parasite due to significant activity against L. amazonensis and L. infantum promastigote forms (IC50 = 14.6 and 31.7 M for L. amazonensis PH8 and Josefa strains, respectively, and 11.3 M for L. infantum) and intracellular amastigotes (IC50 values = 14.2 and 16.6 M for PH8 and Josefa strains, respectively, and 21.7 M for L. infantum). Leishmania parasites treated with TPCK presented mitochondrial alterations, oxidative stress, modifications in lipid content, flagellar alterations, and cytoplasmic vacuoles, all of which are factors that could be considered as contributing to the death of the parasites. Furthermore, BALB/c mice infected with L. amazonensis and treated with TPCK had a reduction in lesion size and parasite loads in the footpad and spleen. In BALB/c mice infected with L. infantum, TPCK also caused a reduction in the parasite loads in the liver and spleen. Therefore, we highlight the antileishmanial effect of the assessed serine protease inhibitor, proposing a potential therapeutic target in Leishmania as well as a possible new alternative treatment for leishmaniasis.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/54653/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALPatriciaMachado+HerbertGuedes_etal_IOC_2022.pdfPatriciaMachado+HerbertGuedes_etal_IOC_2022.pdfapplication/pdf9203057https://www.arca.fiocruz.br/bitstream/icict/54653/2/PatriciaMachado%2bHerbertGuedes_etal_IOC_2022.pdf8986f193c156565a0b86f22666d915e6MD52icict/546532022-08-16 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dc.title.pt_BR.fl_str_mv Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
title Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
spellingShingle Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
Machado, Patrícia de A.
Proteases de serina
TPCK
Leishmaniose
Leishmania amazonensis
Leishmania infantum
Serine proteases
TPCK
Leishmaniasis
Leishmania amazonensis
Leishmania infantum
title_short Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
title_full Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
title_fullStr Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
title_full_unstemmed Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
title_sort Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
author Machado, Patrícia de A.
author_facet Machado, Patrícia de A.
Gomes, Pollyanna S.
Carneiro, Monique P. D.
Midlej, Victor
Coimbra, Elaine S.
Guedes, Herbert L. de Matos
author_role author
author2 Gomes, Pollyanna S.
Carneiro, Monique P. D.
Midlej, Victor
Coimbra, Elaine S.
Guedes, Herbert L. de Matos
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Machado, Patrícia de A.
Gomes, Pollyanna S.
Carneiro, Monique P. D.
Midlej, Victor
Coimbra, Elaine S.
Guedes, Herbert L. de Matos
dc.subject.other.pt_BR.fl_str_mv Proteases de serina
TPCK
Leishmaniose
Leishmania amazonensis
Leishmania infantum
topic Proteases de serina
TPCK
Leishmaniose
Leishmania amazonensis
Leishmania infantum
Serine proteases
TPCK
Leishmaniasis
Leishmania amazonensis
Leishmania infantum
dc.subject.en.pt_BR.fl_str_mv Serine proteases
TPCK
Leishmaniasis
Leishmania amazonensis
Leishmania infantum
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunobiotecnologia. Rio de Janeiro, RJ, Brasil / Universidade Federal de Juiz de Fora. Núcleo de Pesquisas em Parasitologia. Juiz de Fora, MG, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-08-16T12:26:58Z
dc.date.available.fl_str_mv 2022-08-16T12:26:58Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MACHADO, Patrícia de A. et al. Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum. Pharmaceutics, v. 14, 1373, p. 1 - 21, June 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/54653
dc.identifier.issn.pt_BR.fl_str_mv 1999-4923
dc.identifier.doi.none.fl_str_mv 10.3390/ pharmaceutics14071373
identifier_str_mv MACHADO, Patrícia de A. et al. Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum. Pharmaceutics, v. 14, 1373, p. 1 - 21, June 2022.
1999-4923
10.3390/ pharmaceutics14071373
url https://www.arca.fiocruz.br/handle/icict/54653
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv MDPI
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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instacron:FIOCRUZ
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https://www.arca.fiocruz.br/bitstream/icict/54653/2/PatriciaMachado%2bHerbertGuedes_etal_IOC_2022.pdf
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