Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate.

ABSTRACT:

Background and purpose

Choline analogues, a new type of antimalarials, exert potent in vitro and in vivo antimalarial activity. This has given rise to albitiazolium, which is currently in phase II clinical trials to cure severe malaria. Here we dissected its mechanism of action step by step from choline entry into the infected erythrocyte to its effect on phosphatidylcholine (PC) biosynthesis.

Experimental approach

We biochemically unravelled the transport and enzymatic steps that mediate de novo synthesis of PC and elucidated how albitiazolium enters the intracellular parasites and affects the PC biosynthesis.

Key results

Choline entry into Plasmodium falciparum-infected erythrocytes is achieved both by the remnant erythrocyte choline carrier and by parasite-induced

SUBMITTER: Wein S 

PROVIDER: S-EPMC3437492 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature