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

dc.creatorMachado, Patrícia de A.
dc.creatorGomes, Pollyanna S.
dc.creatorCarneiro, Monique P. D.
dc.creatorMidlej, Victor
dc.creatorCoimbra, Elaine S.
dc.creatorGuedes, Herbert L. de Matos
dc.date2022-08-16T12:26:58Z
dc.date2022-08-16T12:26:58Z
dc.date2022
dc.date.accessioned2023-09-26T20:34:43Z
dc.date.available2023-09-26T20:34:43Z
dc.identifierMACHADO, 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.identifier1999-4923
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/54653
dc.identifier10.3390/ pharmaceutics14071373
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8859906
dc.descriptionStudies 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectProteases de serina
dc.subjectTPCK
dc.subjectLeishmaniose
dc.subjectLeishmania amazonensis
dc.subjectLeishmania infantum
dc.subjectSerine proteases
dc.subjectTPCK
dc.subjectLeishmaniasis
dc.subjectLeishmania amazonensis
dc.subjectLeishmania infantum
dc.titleEffects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum
dc.typeArticle


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