Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica.
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.
Seifert
K
K
Division of Specific Prophylaxis and Tropical Medicine, Department of Pathophysiology, University of Vienna, A-1090 Vienna, Austria.
Duchêne
M
M
Wernsdorfer
W H
WH
Kollaritsch
H
H
Scheiner
O
O
Wiedermann
G
G
Hottkowitz
T
T
Eibl
H
H
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*
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008081:Liposomes; D010767:Phosphorylcholine; C039128:miltefosine