Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica

• Published in: Antimicrobial agents and chemotherapy Vol. 45; no. 5; pp. 1505 - 1510
• Main Authors: SEIFERT, Karin, DUCHENE, Michael, WERNSDORFER, Walther H, KOLLARITSCH, Herwig, SCHEINER, Otto, WIEDERMANN, Gerhard, HOTTKOWITZ, Thomas, EIBL, Hansjörg
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.05.2001
• Subjects: alkylphosphocholines; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Chemistry, Pharmaceutical; Drug Carriers; Drug Evaluation, Preclinical; Entamoeba histolytica; Entamoeba histolytica - cytology; Entamoeba histolytica - drug effects; Entamoebiasis - parasitology; Humans; Intestinal Diseases - parasitology; Liposomes; Medical sciences; miltefosine; Pharmacology. Drug treatments; phosphocholines; Phosphorylcholine - administration & dosage; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacology; Susceptibility; Encapsulation; Human; Protozoa; Lobosea; Pharmaceutical technology; Liposome; Phospholipid; Entamoeba histolytica; Drug carrier; In vitro; Biological activity; Miltefosine; Parasiticid; Dosage form; Lysophospholipid; Digestive diseases; Intestinal disease
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.45.5.1505-1510.2001

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 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.