Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

Keith Clinch, Douglas R. Crump, Gary B. Evans, Keith Z. Hazleton, Jennifer M. Mason, Vern L. Schramm, Peter C. Tyler

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme.

Original languageEnglish (US)
Pages (from-to)5629-5646
Number of pages18
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number17
DOIs
StatePublished - Sep 1 2013

Keywords

  • HGXPRTase
  • Malaria
  • Phosphoribosyltransferase
  • Protozoa
  • Purine salvage

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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