6-phosphogluconate dehydrogenase: A target for drugs in African trypanosomes

Stefania Hanau, Eliana Rinaldi, Franco Dallocchio, Ian H. Gilbert, Christophe Dardonville, Margaret J. Adams, Sheila Gover, Michael P. Barrett

    Research output: Contribution to journalReview articlepeer-review

    24 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2639-2650
    Number of pages12
    JournalCurrent Topics in Medicinal Chemistry
    Volume11
    Issue number19
    DOIs
    Publication statusPublished - Oct 2004

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