Your browser doesn't support javascript.
loading
Effects of squalene synthase inhibitors on the growth and ultrastructure of Trypanosoma cruzi.
Braga, Marina V; Urbina, Julio A; de Souza, Wanderley.
Afiliação
  • Braga MV; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha de Fundão, 21949-900 Rio de Janeiro, RJ, Brazil.
Int J Antimicrob Agents ; 24(1): 72-8, 2004 Jul.
Article em En | MEDLINE | ID: mdl-15225865
Squalene synthase (SQS) catalyses the first committed step of sterol biosynthesis; a blockade of this enzyme does not affect the production of other essential isoprenoids. In the present study, 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (BPQ-OH) and ER27856, two specific inhibitors of SQS, were tested against epimastigote forms of Trypanosoma cruzi. Both compounds inhibited parasite multiplication with IC(50) values of 24.3 and 4.5 microM, respectively and induced marked morphological changes. These changes included: (a) detachment of the plasma membrane from the cell body, forming blebs; (b) detachment of the membrane lining the cell body and the flagellum from the sub-pellicular and axonemal microtubules; (c) enlargement of the flagellar pocket; (d) enlargement of a vacuole localised close to the flagellar pocket, which may correspond to a contractile vacuole; (e) mitochondrial swelling, with the appearance of concentric structures formed by invaginations of the inner mitochondrial membrane; (f) alterations in the nucleus of some cells, where the chromatin appears in clumps, as described for apoptotic cells; and (g) blockage of cytokinesis. These alterations are interpreted as a consequence of the depletion of essential parasite sterols induced by the experimental compounds and the concomitant alteration of the physical properties of the parasite membranes.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farnesil-Difosfato Farnesiltransferase / Trypanosoma cruzi / Inibidores Enzimáticos Limite: Animals Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farnesil-Difosfato Farnesiltransferase / Trypanosoma cruzi / Inibidores Enzimáticos Limite: Animals Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda