Effect of a bis-thiazolium compound on the biosynthesis of Plasmodium falciparum phospholipids.

Autor: Ahiboh H; Département de Biochimie Biologie Moléculaire, UFR des Sciences Pharmaceutiques et Biologiques, Université de Cocody - Abidjan BP V34., Djaman AJ, Yapi FH, Edjeme-Aké A, Hauhouot-Attoungbré ML, Yayo ED, Monnet D
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2009 Aug; Vol. 24 (4), pp. 911-7.
DOI: 10.1080/14756360802447974
Abstrakt: 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.
Databáze: MEDLINE
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