First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness

Terry K Smith, Benjamin L. Young, Helen Denton, David L. Hughes, Gerd K. Wagner

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

Drug-like molecules with activity against Trypanosoma brucei are urgently required as potential therapeutics for the treatment of African sleeping sickness. Starting from known inhibitors of other glycosyl-transferases, we have developed the first small molecular inhibitors of dolicholphosphate mannose synthase (DPMS), a mannosyltransferase critically involved in glycoconjugate biosynthesis in T. brucei. We show that these DPMS inhibitors prevent the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, and possess trypanocidal activity against live trypanosomes. (C) 2009 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1749-1752
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number6
DOIs
Publication statusPublished - 15 Mar 2009

Keywords

  • African sleeping sickness
  • Trypanosoma
  • Dolicholphosphate mannose synthase
  • Enzyme inhibitors
  • VARIANT SURFACE GLYCOPROTEIN
  • UDP-GALACTOPYRANOSE MUTASE
  • TRYPANOSOMA-BRUCEI
  • GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS
  • SELECTIVE INHIBITORS
  • ANTIGENIC VARIATION
  • IDENTIFICATION
  • DERIVATIVES
  • ROLES
  • GLYCOSYLTRANSFERASE

Fingerprint

Dive into the research topics of 'First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness'. Together they form a unique fingerprint.

Cite this