Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs

Author(s): M.T. Harris, W.G. Mitchell, J.C. Morris

Journal Name: Current Medicinal Chemistry

Volume 21 , Issue 15 , 2014


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Abstract:

Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.

Keywords: Drug targets, glycolysis, metabolism, protozoa, therapeutics.

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Article Details

VOLUME: 21
ISSUE: 15
Year: 2014
Published on: 30 September, 2013
Page: [1668 - 1678]
Pages: 11
DOI: 10.2174/09298673113206660286
Price: $65

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