Inhibition of hexose transport and abrogation of pH homeostasis in the intraerythrocytic malaria parasite by an O-3-hexose derivative

FEBS Lett. 2004 Jul 16;570(1-3):93-6. doi: 10.1016/j.febslet.2004.06.032.

Abstract

An O-3-hexose derivative, shown previously to inhibit a malaria parasite hexose transporter expressed in Xenopus oocytes as well as to suppress the multiplication of parasites, both in vitro and in vivo, was shown here to block the uptake of hexose sugars into isolated blood-stage parasites. This led to a decline in ATP levels and the loss of intracellular pH control. The results are consistent with those obtained with the cloned transporter. They support the notion that the transporter mediates uptake of glucose into the intraerythrocytic parasite and provide further support for the view that it is a suitable antimalarial drug target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport
  • Dose-Response Relationship, Drug
  • Erythrocytes / metabolism*
  • Glucose / metabolism
  • Glycolysis
  • Hexoses / chemistry*
  • Hexoses / metabolism
  • Hexoses / pharmacokinetics
  • Hydrogen-Ion Concentration
  • Oocytes / metabolism
  • Plasmodium falciparum / metabolism*
  • Time Factors
  • Xenopus

Substances

  • Hexoses
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • Glucose