Modifications around the hydroxamic acid chelating group of fosmidomycin, an inhibitor of the metalloenzyme 1-deoxyxylulose 5-phosphate reductoisomerase (DXR)

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6563-7. doi: 10.1016/j.bmcl.2012.09.021. Epub 2012 Sep 15.

Abstract

Fosmidomycin derivatives in which the hydroxamic acid group has been replaced by several bidentate chelators as potential hydroxamic alternatives were prepared and tested against the DXR from Escherichia coli. These results illustrate the predominant role of the hydroxamate functional group as the most effective metal binding group in DXR inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldose-Ketose Isomerases / antagonists & inhibitors
  • Aldose-Ketose Isomerases / chemistry*
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / enzymology
  • Fosfomycin / analogs & derivatives*
  • Fosfomycin / chemistry
  • Fosfomycin / pharmacology
  • Hydroxamic Acids / chemistry*
  • Inhibitory Concentration 50
  • Metalloproteins / chemistry
  • Molecular Structure
  • Protein Binding / drug effects

Substances

  • Chelating Agents
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Metalloproteins
  • Fosfomycin
  • fosmidomycin
  • 1-deoxy-D-xylulose 5-phosphate reductoisomerase
  • Aldose-Ketose Isomerases