title: Efficacy of anticancer alkylphosphocholines in Trypanosoma brucei subspecies.
abstract: Tetradecylphosphocholine (TPC), hexadecylphosphocholine (HPC), hexadecylphospho(N-N-N-trimethyl)hexanolamine (HPC6), octadecylphosphocholine (OPC), and octadecyl-[2-(N-methylpiperidinio)ethyl]-phosphate (OMPEP) were investigated for antitrypanosomal activity in vitro and in vivo. OMPEP showed the best trypanocidal efficacy in vitro; it was superior to the model compound HPC and comparable to the reference compound alpha-DFMO. HPC showed moderate activity in vivo in terms of increased life expectancy (up to 35% in the acute NMRI-mouse model or 49% if combined with phenylbutazone) and increased packed cell volume, if administered daily. However, HPC and the other alkylphosphocholines failed to prolong survival time of treated mice if given intermittently. Phenylbutazone had no own trypanocidal effect but increased the efficacy of alkylphosphocholines in vitro and in vivo: the combination of HPC and phenylbutazone acted apparently synergistic.
authors.affiliation: AG Toxikologie und Chemotherapie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: S M
authors.initials: SM
authors.lastname: Konstantinov
authors.forename: R
authors.initials: R
authors.lastname: Kaminsky
authors.forename: R
authors.initials: R
authors.lastname: Brun
authors.forename: M R
authors.initials: MR
authors.lastname: Berger
authors.forename: U
authors.initials: U
authors.lastname: Zillmann
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010653:Phenylbutazone / Q000008:administration & dosage / Q000627:therapeutic use; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D010880:Piperidines; D010972:Platelet Activating Factor; D010767:Phosphorylcholine; C073010:1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphono(N,N,N-trimethyl)hexanolamine; C084837:octadecyl-(2-(N-methylpiperidino)ethyl)phosphate; C039128:miltefosine; C032164:n-octadecylphosphocholine; C031166:n-tetradecylphosphorylcholine; D010653:Phenylbutazone