title: 6-phosphogluconate dehydrogenase: a target for drugs in African trypanosomes.
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, non-carbohydrate 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.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Hanau
authors.forename: Eliana
authors.initials: E
authors.lastname: Rinaldi
authors.forename: Franco
authors.initials: F
authors.lastname: Dallocchio
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
authors.forename: Christophe
authors.initials: C
authors.lastname: Dardonville
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Adams
authors.forename: Sheila
authors.initials: S
authors.lastname: Gover
authors.forename: Michael P
authors.initials: MP
authors.lastname: Barrett
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D010734:Phosphogluconate Dehydrogenase