This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Urbina, J. A.
Right arrow Articles by Docampo, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Urbina, J. A.
Right arrow Articles by Docampo, R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2003, p. 2047-2050, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.2047-2050.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mechanism of Action of 4-Phenoxyphenoxyethyl Thiocyanate (WC-9) against Trypanosoma cruzi, the Causative Agent of Chagas’ Disease{dagger}

Julio A. Urbina,1* Juan Luis Concepcion,2 Andrea Montalvetti,3 Juan B. Rodriguez,4 and Roberto Docampo3

Laboratorio de Quimica Biológica, Centro de Bioquimica y Biofisica, Instituto Venezolano de Investigaciones Cientificas, Carretera Panamericana, Caracas 1020,1 Laboratorio de Enzimología de Parásitos, Departamento de Biologia, Facultad de Ciencias, Universidad de Los Andes, La Hechicera, Merida, Venezuela,2 Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802,3 Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, RA-1428 Buenos Aires, Argentina4

Received 2 December 2002/ Returned for modification 14 January 2003/ Accepted 6 March 2003

We investigated the molecular basis of the activity of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the etiological agent of Chagas’ disease. We found that growth inhibition of T. cruzi epimastigotes induced by this compound was associated with a reduction in the content of the parasite's endogenous sterols due to a specific blockade of their de novo synthesis at the level of squalene synthase.

* Corresponding author. Mailing address: Laboratorio de Quimica Biológica, Centro de Bioquimica y Biofisica, Instituto Venezolano de Investigaciones Cientificas, Altos de Pipe, Km. 11, Carretera Panamericana, Caracas 1020, Venezuela. Phone: (58-212)-5041660. Fax: (58-212)-5041093. E-mail: jaurbina{at}ivic.ve.

{dagger} We dedicate this paper to the memory of Zigman Brener, pioneer in experimental chemotherapy studies of Chagas’ disease.

Antimicrobial Agents and Chemotherapy, June 2003, p. 2047-2050, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.2047-2050.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Urbina, J. A., Concepcion, J. L., Caldera, A., Payares, G., Sanoja, C., Otomo, T., Hiyoshi, H. (2004). In Vitro and In Vivo Activities of E5700 and ER-119884, Two Novel Orally Active Squalene Synthase Inhibitors, against Trypanosoma cruzi. Antimicrob. Agents Chemother. 48: 2379-2387 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»