Effect of a bis-thiazolium compound on the biosynthesis of Plasmodium falciparum phospholipids.
In the eukaryotic cell, phospholipids can be biosynthesized by two pathways, one from choline and the other one from ethanolamine. The functional effectiveness of each pathway depends on the type of the cell. Thiazolium designed-drugs have shown, under in vivo conditions, antiplasmodial and antimalarial activities with inhibition of the phospholipids biosynthesis. This study aimed to discover the pathways involved in the biosynthesis of phospholipids in Plasmodium and deduce the biochemical steps inhibited by T4, a bis-thiazolium bromide drug. We compared the uptake of radiolabeled precursors and their selective incorporation in the phospholipids of cultured Plasmodium-infected and -uninfected erythrocytes which revealed that phosphatidylcholine of Plasmodium is synthesized both from choline and ethanolamine (4.7 vs 1.9 nmol/10(10) cells x h(-1)). T4 has no effect on the biosynthesis of phosphatidylethanolamine but T4 inhibited, in a selective way, the in vitro uptake of choline. However no enzymes in the biosynthesis of phospholipids seem to be inhibited by T4 but rather an inhibition of choline entry into the parasite.
Ahiboh
Hugues
H
Département de Biochimie Biologie Moléculaire, UFR des Sciences Pharmaceutiques et Biologiques, Université de Cocody - Abidjan BP V34.
Djaman
Allico J
AJ
Yapi
Félix H
FH
Edjeme-Aké
Angèle
A
Hauhouot-Attoungbré
Marie-Laure
ML
Yayo
Eric D
ED
Monnet
Dagui
D
D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*
D000962:Antimalarials; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013844:Thiazoles; C483858:phosphatidylethanolamine