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 Seifert, K.
Right arrow Articles by Eibl, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seifert, K.
Right arrow Articles by Eibl, H.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2001, p. 1505-1510, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1505-1510.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Effects of Miltefosine and Other Alkylphosphocholines on Human Intestinal Parasite Entamoeba histolytica

Karin Seifert,1 Michael Duchêne,1,* Walther H. Wernsdorfer,1 Herwig Kollaritsch,1 Otto Scheiner,2 Gerhard Wiedermann,1 Thomas Hottkowitz,3 and Hansjörg Eibl3

Division of Specific Prophylaxis and Tropical Medicine1 and Division of Applied Experimental Pathology,2 Department of Pathophysiology, University of Vienna, A-1090 Vienna, Austria, and Max-Planck-Institute of Biophysical Chemistry, D-37077 Göttingen, Germany3

Received 1 November 2000/Returned for modification 18 December 2000/Accepted 12 February 2001

The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery and liver abscess. It is therefore responsible for significant morbidity and mortality in a number of countries. Infections with E. histolytica are treated with nitroimidazoles, primarily with metronidazole. At this time, there is a lack of useful alternative classes of substances for the treatment of invasive amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine) were originally developed as antitumor agents, but recently they have been successfully used for the treatment of visceral leishmaniasis in humans. We examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with and without double bond(s), for their activity against two strains of E. histolytica. The compounds with the highest activity were oleyl-PC, octadecyl-PC, and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment between 15 and 21 µM for strain SFL-3 and between 73 and 98 µM for strain HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are expected to be well tolerated. Liposomal formulations of oleyl-PC or closely related alkyl-PCs could be promising candidates for testing as broad-spectrum antiprotozoal and antitumor agents in humans.

* Corresponding author. Mailing address: Division of Specific Prophylaxis and Tropical Medicine, Department of Pathophysiology, Vienna General Hospital, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: (43-1) 40400-5108. Fax: (43-1) 40400-5130. E-mail: michael.duchene{at}univie.ac.at.

Antimicrobial Agents and Chemotherapy, May 2001, p. 1505-1510, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1505-1510.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Walochnik, J., Obwaller, A., Gruber, F., Mildner, M., Tschachler, E., Suchomel, M., Duchene, M., Auer, H. (2009). Anti-Acanthamoeba efficacy and toxicity of miltefosine in an organotypic skin equivalent. J Antimicrob Chemother 64: 539-545 [Abstract] [Full Text]  
  • McBride, J., Mullen, A. B., Carter, K. C., Roberts, C. W. (2007). Differential cytotoxicity of phospholipid analogues to pathogenic Acanthamoeba species and mammalian cells. J Antimicrob Chemother 60: 521-525 [Abstract] [Full Text]  
  • Llull, D., Rivas, L., Garcia, E. (2007). In Vitro Bactericidal Activity of the Antiprotozoal Drug Miltefosine against Streptococcus pneumoniae and Other Pathogenic Streptococci. Antimicrob. Agents Chemother. 51: 1844-1848 [Abstract] [Full Text]  
  • Blaha, C., Duchene, M., Aspock, H., Walochnik, J. (2006). In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis. J Antimicrob Chemother 57: 273-278 [Abstract] [Full Text]  
  • Ordaz-Pichardo, C., Shibayama, M., Villa-Trevino, S., Arriaga-Alba, M., Angeles, E., de la Garza, M. (2005). Antiamoebic and Toxicity Studies of a Carbamic Acid Derivative and Its Therapeutic Effect in a Hamster Model of Hepatic Amoebiasis. Antimicrob. Agents Chemother. 49: 1160-1168 [Abstract] [Full Text]  
  • Paris, C., Loiseau, P. M., Bories, C., Breard, J. (2004). Miltefosine Induces Apoptosis-Like Death in Leishmania donovani Promastigotes. Antimicrob. Agents Chemother. 48: 852-859 [Abstract] [Full Text]  
  • Sannella, A., Gradoni, L., Persichini, T., Ongini, E., Venturini, G., Colasanti, M. (2003). Intracellular Release of Nitric Oxide by NCX 972, an NO-Releasing Metronidazole, Enhances In Vitro Killing of Entamoeba histolytica. Antimicrob. Agents Chemother. 47: 2303-2306 [Abstract] [Full Text]  
  • Saraiva, V. B., Gibaldi, D., Previato, J. O., Mendonca-Previato, L., Bozza, M. T., Freire-de-Lima, C. G., Heise, N. (2002). Proinflammatory and Cytotoxic Effects of Hexadecylphosphocholine (Miltefosine) against Drug-Resistant Strains of Trypanosoma cruzi. Antimicrob. Agents Chemother. 46: 3472-3477 [Abstract] [Full Text]  
  • Walochnik, J., Duchene, M., Seifert, K., Obwaller, A., Hottkowitz, T., Wiedermann, G., Eibl, H., Aspock, H. (2002). Cytotoxic Activities of Alkylphosphocholines against Clinical Isolates of Acanthamoeba spp.. Antimicrob. Agents Chemother. 46: 695-701 [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»