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

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 glycosyltransferases, 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.
AuthorsTerry K Smith, Benjamin L Young, Helen Denton, David L Hughes, Gerd K Wagner
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 6 Pg. 1749-52 (Mar 15 2009) ISSN: 1464-3405 [Electronic] England
PMID19217283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ethanol
  • Mannosyltransferases
  • dolichyl-phosphate beta-D-mannosyltransferase
  • Animals
  • Chemistry, Pharmaceutical (methods)
  • Crystallography, X-Ray (methods)
  • Drug Design
  • Drug Evaluation, Preclinical
  • Ethanol (chemistry)
  • Humans
  • Mannosyltransferases (antagonists & inhibitors, chemistry)
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Trypanosoma brucei brucei (enzymology)
  • Trypanosomiasis, African (drug therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: