Author | Braga, Marina V. | |
Author | Souza, Wanderley sw | |
Access date | 2020-01-01T19:07:45Z | |
Available date | 2020-01-01T19:07:45Z | |
Document date | 2006 | |
Citation | BRAGA, Marina Vianna; SOUZA, W\anderley de. Efects of protein kinase and phosphatidylinositol-3kinase inhibitors on growth and ultrastructure of Trypanosoma cruzi. FEMS Microbiology Letters, v. 256, p. 209-216, 2006. | pt_BR |
ISSN | 0378-1097 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/38928 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Tripanossomático | pt_BR |
Subject in Portuguese | Inibidor da proteína quinase | pt_BR |
Subject in Portuguese | Quimioterapia | pt_BR |
Subject in Portuguese | Ultraestrutura | pt_BR |
Title | Effects of protein kinase and phosphatidylinositol-3 kinase inhibitors on growth and ultrastructure of Trypanosoma cruzi | pt_BR |
Type | Article | pt_BR |
DOI | 10.1111/j.1574-6968.2006.00125.x | |
Abstract | An increasing number of protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. Some PK inhibitors display antiproliferative effects on protozoa. We tested three PK inhibitors on the growth and ultrastructure of epimastigotes of Trypanosoma cruzi and the effect of these drugs on intracellular amastigotes. They were staurosporine (serine/threonine kinase inhibitor), genistein (tyrosine kinase inhibitor), and wortmannin (phosphatidylinositol 3' (PI3) kinase inhibitor). All drugs inhibited epimastigote growth at the concentrations tested. Wortmannin inhibited parasite growth at the lowest concentrations. However, staurosporine was the most effective after 24 h treatment and genistein caused the stronger inhibition during the whole treatment (60-70% inhibition). The IC50 were: staurosporine: 6.43+/-1.28 microM; genistein: 6.54+/-1.86 microM; and wortmannin: 0.056+/-0.014 microM. These PK inhibitors had strong ultrastructural effects on the epimastigotes: abnormal chromatin condensation of the nucleus; loose flagellar membrane with the formation of blebs; incomplete cell division; autophagosomes and myelin-like figures. These drugs did not interfere with the division of intracellular amastigotes or with its differentiation to trypomastigotes. However, as trypanosomes have kinomes that contain a large set of protein kinases and phosphatases, PKs should not be disregarded as an important target for chemotherapy of Chagas disease. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Trypanosomatid | pt_BR |
Subject | Protein kinase inhibitor | pt_BR |
Subject | Chemotherapy | pt_BR |
Subject | Ultrastructure. | pt_BR |
e-ISSN | 1574-6968 | |
Embargo date | 2025-01-01 | |