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6-Phosphogluconate Dehydrogenase: A Target for Drugs in African Trypanosomes

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Abstract:

New drugs are urgently required for Human African Trypanosomiasis (sleeping sickness), a disease which has re-emerged as a major health threat in Sub-Saharan Africa. The third enzyme of the pentose phosphate pathway, 6-phosphogluconate dehydrogenase, has been shown to be a good target for drugs. The enzyme is essential to the trypanosomes that causes sleeping sickness and structural differences when compared to its mammalian counterpart allow for selective inhibition. Three series of inhibitors have been designed, these include phosphorylated carbohydrate substrate and transition state analogues, noncarbohydrate substrate analogues and also triphenylmethane-based compounds. All have shown selective inhibition of the trypanosomal 6-phosphogluconate dehydrogenase and representatives of each have trypanocidal activity.

Keywords: 6- phosphogluconate dehydrogenase; chemotherapy; drugs; human african trypanosomiasis; pentose phosphate pathway; sleeping sickness; transition state inhibitor; triphenylmethane

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043364441

Affiliations: Institute of Biomedical and Life Sciences, Division of Infection & Immunity, University of Glasgow, The Joseph Black Building, Glasgow, G12 8QQ, UK.

Publication date: October 1, 2004

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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