| Author | Machado, Patrícia de A. | |
| Author | Gomes, Pollyanna S. | |
| Author | Carneiro, Monique P. D. | |
| Author | Midlej, Victor | |
| Author | Coimbra, Elaine S. | |
| Author | Guedes, Herbert L. de Matos | |
| Access date | 2022-08-16T12:26:58Z | |
| Available date | 2022-08-16T12:26:58Z | |
| Document date | 2022 | |
| Citation | 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. | pt_BR |
| ISSN | 1999-4923 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/54653 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Proteases de serina | pt_BR |
| Subject in Portuguese | TPCK | pt_BR |
| Subject in Portuguese | Leishmaniose | pt_BR |
| Subject in Portuguese | Leishmania amazonensis | pt_BR |
| Subject in Portuguese | Leishmania infantum | pt_BR |
| Title | Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum | pt_BR |
| Type | Article | |
| DOI | 10.3390/ pharmaceutics14071373 | |
| Abstract | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Núcleo de Pesquisas em Parasitologia. Juiz de Fora, MG, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Subject | Serine proteases | pt_BR |
| Subject | TPCK | pt_BR |
| Subject | Leishmaniasis | pt_BR |
| Subject | Leishmania amazonensis | pt_BR |
| Subject | Leishmania infantum | pt_BR |
