title: Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica.
abstract: 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 microM for strain SFL-3 and between 73 and 98 microM 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.
authors: Division of Specific Prophylaxis and Tropical Medicine, Department of Pathophysiology, University of Vienna, A-1090 Vienna, Austria.
authors: K
authors: K
authors: Seifert
authors: M
authors: M
authors: Duchêne
authors: W H
authors: WH
authors: Wernsdorfer
authors: H
authors: H
authors: Kollaritsch
authors: O
authors: O
authors: Scheiner
authors: G
authors: G
authors: Wiedermann
authors: T
authors: T
authors: Hottkowitz
authors: H
authors: H
authors: Eibl
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004748:Entamoeba histolytica / Q000166:cytology / Q000187:drug effects*; D004749:Entamoebiasis / Q000469:parasitology; D006801:Humans; D007410:Intestinal Diseases / Q000469:parasitology*; D008081:Liposomes; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008081:Liposomes; D010767:Phosphorylcholine; C039128:miltefosine