6-phosphogluconate dehydrogenase: a target for drugs in African trypanosomes.
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.
Hanau
Stefania
S
Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Italy.
Rinaldi
Eliana
E
Dallocchio
Franco
F
Gilbert
Ian H
IH
Dardonville
Christophe
C
Adams
Margaret J
MJ
Gover
Sheila
S
Barrett
Michael P
MP
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*
D004791:Enzyme Inhibitors; D010734:Phosphogluconate Dehydrogenase