Effect of alkyl-lysophospholipids on some aspects of the metabolism of Leishmania donovani.
Alkyl-lysophospholipids (ALPs), developed initially to be antitumor agents, have proved highly effective in the treatment of visceral leishmaniasis, a disease caused by the species making up the protozoan complex Leishmania donovani. Although their effectiveness is known, the mode of action against this parasite is not completely understood. In the present work, we have studied the effect of 3 derivatives, edelfosine, miltefosine, and ilmofosine. Using nuclear magnetic resonance spectroscopy ('H-NMR), we have examined the excreted catabolites from glucose metabolism in the promastigote forms treated with these compounds. The ALPs at concentrations of 19 and 38 microM inhibit the excretion of acetate, succinate, and pyruvate. The effect of edelfosine, miltefosine, and ilmofosine on the activity of the enzymes hexokinase, glycerolkinase 3-PD, phosphoglucose isomerase, superoxide dismutase, and phospholipase C were also examined. Glycerolkinase 3-PD and phosphoglucose isomerase are generally insensitive to the compounds, whereas hexokinase and superoxide dismutase are inhibited by miltefosine and ilmofosine. The ALPs exhibited an activated effect against the phospholipase C activity. Alkyl-lysophospholipids were shown to have a significant effect on several enzymes in important biochemical pathways indispensable for the survival of L. donovani promasigotes.
Azzouz
S
S
Institute of Biotechnology, Department of Parasitology, Faculty of Sciences Campus Fuentenueva CP, Granada, Spain.
Maache
M
M
Sánchez-Moreno
M
M
Petavy
A F
AF
Osuna
A
A
D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development / Q000648:ultrastructure; D009682:Magnetic Resonance Spectroscopy; D021261:Parasitic Sensitivity Tests; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015800:Protozoan Proteins / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects; D010738:Type C Phospholipases / Q000187:drug effects
D010742:Phospholipid Ethers; D015800:Protozoan Proteins; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine; C043297:ilmofosine; D013482:Superoxide Dismutase; D010738:Type C Phospholipases