EFFICACY OF ANTICANCER ALKYLPHOSPHOCHOLINES IN TRYPANOSOMA-BRUCEI SUBSPECIES

Tetradecylphosphocholine (TPC), hexadecylphosphocholine (HPC), hexadec ylphospho(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 al pha-DFMO. HPC showed moderate activity in vivo in terms of increased l ife expectancy (up to 35% in the acute NMRI-mouse model or 49% if comb ined with phenylbutazone) and increased packed cell volume, if adminis tered daily. However, HPC and the other alkylphosphocholines failed to prolong survival time of treated mice if given intermittently. Phenyl butazone 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. (C) 1997 Elsevier Science B.V.