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

Catherine Zinglé; Lionel Kuntz; Denis Tritsch; Catherine Grosdemange-Billiard; Michel Rohmer

doi:10.1016/j.bmcl.2012.09.021

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.

Authors

Catherine Zinglé¹, Lionel Kuntz, Denis Tritsch, Catherine Grosdemange-Billiard, Michel Rohmer

Affiliation

¹ Université de Strasbourg/CNRS, Strasbourg, UMR 7177, Institut Le Bel, 4 rue Blaise Pascal 67081, Strasbourg, France.

PMID: 23025997
DOI: 10.1016/j.bmcl.2012.09.021

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Fosmidomycin derivatives in which the hydroxamic acid group has been replaced by several bidentate chelators as potential hydroxamic alternatives were prepared and tested against the DXR from Escherichia coli.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