1. First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness
- Author
-
Gerd K. Wagner, Helen Denton, Terry K. Smith, Benjamin L. Young, and David L. Hughes
- Subjects
Mannosyltransferase ,Glycoconjugate ,Chemistry, Pharmaceutical ,Trypanosoma brucei brucei ,Clinical Biochemistry ,Drug Evaluation, Preclinical ,Molecular Conformation ,Pharmaceutical Science ,Mannose ,Biology ,Trypanosoma brucei ,Mannosyltransferases ,Crystallography, X-Ray ,Biochemistry ,Article ,chemistry.chemical_compound ,parasitic diseases ,Drug Discovery ,medicine ,Animals ,Humans ,African trypanosomiasis ,Molecular Biology ,chemistry.chemical_classification ,Ethanol ,Molecular Structure ,Organic Chemistry ,Kinetoplastida ,biology.organism_classification ,medicine.disease ,Trypanosomiasis, African ,Models, Chemical ,chemistry ,Drug Design ,Trypanosoma ,Molecular Medicine - 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 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.
- Published
- 2009
- Full Text
- View/download PDF