Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
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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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 |
format |
article |
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 |
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eng |
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eng |
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MDPI |
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MDPI |
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