The inhibitory effect of 2-halo derivatives of D-glucose on glycolysis and on the proliferation of the human malaria parasite Plasmodium falciparum.

The Journal of Pharmacology and Experimental Therapeutics
Donelly A van SchalkwykKevin J Saliba

Abstract

The intraerythrocytic stage of the human malaria parasite Plasmodium falciparum relies on glycolysis for ATP generation, and because it has no energy stores, a constant supply of glucose is necessary for the parasite to grow and multiply. The 2-substituted glucose analogs 2-deoxy-D-glucose (2-DG) and 2-fluoro-2-deoxy-D-glucose (2-FG) have been previously shown to inhibit the in vitro growth of P. falciparum and have been suggested to do so by inhibiting glycosylation in the parasite. In this study, we have investigated the antiplasmodial mechanism of action of 2-DG and 2-FG and compared it with that of other 2-substituted-glucose analogs. The compounds tested inhibited parasite growth to varying degrees, with 2-FG being the most effective. The antiplasmodial activity of some, but not all, of the analogs could be altered by varying the glucose concentration in the culture medium, increasing the antiplasmodial activity of the analogs as the glucose concentration is reduced. A trend was observed between the antiplasmodial activity of these analogs and their ability to inhibit glucose accumulation, glucose phosphorylation by hexokinase, and cytosolic pH regulation within the intraerythrocytic stage of the parasite. Our data are con...Continue Reading

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Citations

Jun 28, 2013·Nature Communications·Xie Wah Audrey ChanKevin J Saliba
May 30, 2013·Antimicrobial Agents and Chemotherapy·Michael T HarrisJames C Morris
Mar 29, 2013·PloS One·Donelly A van SchalkwykKiaran Kirk
Nov 22, 2013·Antioxidants & Redox Signaling·Lihui WangKatja Becker
May 29, 2012·IUBMB Life·Janina PreussKatja Becker
Aug 26, 2014·Molecular Microbiology·Adele M LehaneKiaran Kirk
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Jan 8, 2017·Free Radical Biology & Medicine·Franziska MohringKatja Becker
Jul 28, 2016·Antimicrobial Agents and Chemotherapy·Mindy I DavisJames C Morris
Aug 31, 2016·Antimicrobial Agents and Chemotherapy·Erik L AllmanManuel Llinás
Feb 26, 2020·Antimicrobial Agents and Chemotherapy·Donelly A van SchalkwykColin J Sutherland
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