Transition state analogue inhibitors of protozoan nucleoside hydrolases

Richard H. Furneaux, Vern L. Schramm, Peter C. Tyler

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are potential therapeutic agents for the control of protozoan infections. A series of 1,4-dideoxy-1,4-imino-D-ribitols bearing C- bonded aromatic substituents at C-1 have been synthesized, following carbanion additions to the imine 2, and tested as potential nucleoside hydrolase inhibitors. Nucleoside analogues 8, 11, 14, 17, 20, 24-26, 28 exhibit K(i) values in the range 0.2-22 μM against two representative isozymes of protozoan nucleoside hydrolases. (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)2599-2606
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume7
Issue number11
DOIs
StatePublished - Nov 1999

Fingerprint

N-Glycosyl Hydrolases
Salvaging
Bearings (structural)
Ribitol
Protozoan Infections
Protozoa
Purines
Mammals
Imines
Enzymes
Nucleosides
Isoenzymes
Parasites
purine
Therapeutics

Keywords

  • Antibiotics
  • Antiparasitics
  • Enzyme inhibitors
  • Nucleosides

ASJC Scopus subject areas

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

Cite this

Transition state analogue inhibitors of protozoan nucleoside hydrolases. / Furneaux, Richard H.; Schramm, Vern L.; Tyler, Peter C.

In: Bioorganic and Medicinal Chemistry, Vol. 7, No. 11, 11.1999, p. 2599-2606.

Research output: Contribution to journalArticle

Furneaux, Richard H. ; Schramm, Vern L. ; Tyler, Peter C. / Transition state analogue inhibitors of protozoan nucleoside hydrolases. In: Bioorganic and Medicinal Chemistry. 1999 ; Vol. 7, No. 11. pp. 2599-2606.
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