Effects of squalene synthase inhibitors on the growth and ultrastructure of Trypanosoma cruzi

International Journal of Antimicrobial Agents
Marina V BragaWanderley de Souza

Abstract

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...Continue Reading

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Citations

May 8, 2007·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Marina V BragaWanderley de Souza
Jun 23, 2005·Omics : a Journal of Integrative Biology·Diana M OliveiraUNKNOWN PROGENE, The Brazilian Northeast Genome Program
Aug 22, 2007·Antimicrobial Agents and Chemotherapy·Simon B CammererIan H Gilbert
Sep 4, 2012·Parasitology Research·Fabiana Oliveira Dos Santos GomesIvan da Rocha Pitta
Dec 10, 2008·Expert Opinion on Therapeutic Targets·Maria Nazaré C Soeiro, Solange L de Castro
Feb 9, 2016·European Journal of Medicinal Chemistry·Paulo André Teixeira de Moraes GomesAna Cristina Lima Leite
Apr 22, 2009·The International Journal of Biochemistry & Cell Biology·Wanderley de SouzaJuliany C F Rodrigues
Oct 14, 2008·Micron : the International Research and Review Journal for Microscopy·Rubem F S Menna-BarretoSolange L de Castro
May 6, 2008·Molecular and Biochemical Parasitology·Patricio PortalCristina Paveto
Mar 21, 2007·Veterinary Parasitology·Ana Claudia GranthonWanderley de Souza
Mar 28, 2008·Molecular Systems Biology·Arvind K ChavaliJason A Papin
Aug 15, 2009·Interdisciplinary Perspectives on Infectious Diseases·Wanderley de Souza, Juliany Cola Fernandes Rodrigues
Jan 27, 2006·FEMS Microbiology Letters·Isabella Vieira Palmié-PeixotoMaria Cristina Machado Motta
Jun 14, 2016·European Journal of Medicinal Chemistry·Paulo André Teixeira de Moraes GomesAna Cristina Lima Leite
Feb 8, 2018·Memórias do Instituto Oswaldo Cruz·Carlos Eduardo Sampaio GuedesPatricia Sampaio Tavares Veras
Aug 15, 2019·Expert Opinion on Drug Discovery·Fernando Villalta, Girish Rachakonda
Aug 8, 2020·Frontiers in Cellular and Infection Microbiology·Danielle de Sousa LopesJane Lima-Santos
Jun 3, 2017·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Tatiana Rodrigues AlexandreAndre Gustavo Tempone
Feb 2, 2008·Journal of Medicinal Chemistry·Scott J Hecker, Mark D Erion

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