Metabolic pathways that extract energy from carbon compounds are essential for an organism’s
survival. Therefore, inhibition of enzymes in these pathways represents a potential therapeutic
strategy to combat parasitic infections. However, the high degree of similarity between host and parasite
enzymes makes this strategy potentially difficult. Nevertheless, several existing drugs to treat infections
by parasitic helminths (worms) target metabolic enzymes. These include the trivalent antimonials
that target phosphofructokinase and Clorsulon that targets phosphoglycerate mutase and
phosphoglycerate kinase. Glycolytic enzymes from a variety of helminths have been characterised
biochemically, and some inhibitors identified. To date none of these inhibitors have been developed into therapies. Many
of these enzymes are externalised from the parasite and so are also of interest in the development of potential vaccines.
Less work has been done on tricarboxylic acid cycle enzymes and oxidative phosphorylation complexes. Again, while
some inhibitors have been identified none have been developed into drug-like molecules. Barriers to the development of
novel drugs targeting metabolic enzymes include the lack of experimentally determined structures of helminth enzymes,
lack of direct proof that the enzymes are vital in the parasites and lack of cell culture systems for many helminth species.
Nevertheless, the success of Clorsulon (which discriminates between highly similar host and parasite enzymes) should inspire
us to consider making serious efforts to discover novel anthelminthics, which target metabolic enzymes.
Keywords: Glycolysis, neglected tropical disease, Clorsulon, trematode, nematode, cestode.
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