Inhibitors of UDP-galactopyranose mutase thwart mycobacterial growth

J Am Chem Soc. 2008 May 28;130(21):6706-7. doi: 10.1021/ja8018687. Epub 2008 May 1.


Galactofuranose (Galf) residues are fundamental components of the cell wall of mycobacteria. A key enzyme, UDP-galactopyranose mutase (UGM), that participates in Galf incorporation mediates isomerization of UDP-Galf from UDP-galactopyranose (UDP-Galp). UGM is of special interest as a therapeutic target because the gene encoding it is essential for mycobacterial viability and there is no comparable enzyme in humans. We used structure-activity relationships and molecular design to devise UGM inhibitors. From a focused library of synthetic aminothiazoles, several compounds that block the UGM from Klebsiella pneumoniae or Mycobacterium tuberculosis were identified. These inhibitors block the growth of M. smegmatis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Intramolecular Transferases / antagonists & inhibitors*
  • Intramolecular Transferases / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology*
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology


  • Enzyme Inhibitors
  • Thiazoles
  • Thiazolidines
  • Intramolecular Transferases
  • UDP-galactopyranose mutase