Cytotoxicity of ester and ether lysophospholipids on Leishmania donovani promastigotes.
The cytotoxic activity of four ester lysophospholipids, three ether lysophospholipids, and two radylglycerols on Leishmania donovani promastigotes was determined by measuring the inhibition of cell growth. The 1-acyl lysophospholipids reduced cell growth to 50% of controls at concentrations of 6.4-10.9 microM. In contrast, 1-O-alkenyl-sn-glycero-3-phosphoethanolamine, 1-O-hexadecyl-sn-glycero-3-phosphocholine, and 1-O-hexadecyl-sn-glycerol already showed a 50% inhibition of growth at concentrations between 2.1 and 2.8 microM. Moreover, the unnatural alkyl lysophospholipid analogue 1-O-octadecyl-2-methoxy-sn-glycero-3-phosphocholine was even 10-fold more toxic. Incubations of L. donovani promastigotes with radioactively labelled ether lysophospholipids revealed a rapid uptake of these compounds and their incorporation into cellular lipids at a non-toxic concentration of 1.0 microM. An accumulation of the lysophospholipids in the cell due to insufficient metabolism may be the cause of its cytotoxic effect. The sensitivity of L. donovani cells towards ether lysophospholipids was found to be similar to that reported for tumor cells.
D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004952:Esters / Q000494:pharmacology*; D004987:Ethers / Q000494:pharmacology*; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008246:Lysophospholipids; D009994:Osmolar Concentration; D010743:Phospholipids / Q000378:metabolism / Q000494:pharmacology*
D002264:Carboxylic Acids; D004952:Esters; D004987:Ethers; D008246:Lysophospholipids; D010743:Phospholipids