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3-Bromopyruvate as a potential pharmaceutical in the light of experimental data.
Postȩpy Higieny i Medycyny Doświadczalnej 2017 December 9
3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase). Two cases of clinical application of this compound in the treatment of advanced cancers were reported. By using 3-BrPA, rheumatoid arthritis in SKG mice has been reduced. This compound has also antiparasitic activity: lowers cell viability of Trypanosoma brucei, decreases intracellular proliferation of Toxoplasma gondii and reduces the metabolic activity of Schistosoma mansoni. It also has antifungal properties; particularly it acts strongly on Cryptococcus neoformans, as well as Saccharomyces cerevisiae. An inhibitory effect on bacterial enzymes was also described on: isocitrate lyase from Escherichia coli, Mycobacterium tuberculosis, Pseudomonas indigofera and 2-methylisocitrate lyase, succinate dehydrogenase and acetohydroxylic acid synthase from Escherichia coli. Wherever undesirable (cancer, parasitic) cells differ from normal by more intense glycolysis and higher energy needs, there is a good chance of successful 3-BrPA use. However, this compound acts on all cells and it, therefore, seems that its future as a pharmaceutical is dependent upon the development of appropriate methods for its effective and safe application.
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