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

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

Volume: 11 Issue: 19

Author(s): Stefania Hanau, Eliana Rinaldi, Franco Dallocchio, Ian H. Gilbert, Christophe Dardonville, Margaret J. Adams, Sheila Gover and Michael P. Barrett

Affiliation:

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

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.

Cite this article as:

Hanau Stefania, Rinaldi Eliana, Dallocchio Franco, Gilbert H. Ian, Dardonville Christophe, Adams J. Margaret, Gover Sheila and Barrett P. Michael, 6-Phosphogluconate Dehydrogenase: A Target for Drugs in African Trypanosomes, Current Medicinal Chemistry 2004; 11 (19) . https://dx.doi.org/10.2174/0929867043364441