Pyrazolopyrimidinediones are selective agents for Helicobacter pylori that suppress growth through inhibition of glutamate racemase (MurI)

Antimicrob Agents Chemother. 2009 Aug;53(8):3331-6. doi: 10.1128/AAC.00226-09. Epub 2009 May 11.

Abstract

Pyrazolopyrimidinediones are a novel series of compounds that inhibit growth of Helicobacter pylori specifically. Using a variety of methods, advanced analogues were shown to suppress the growth of H. pylori through the inhibition of glutamate racemase, an essential enzyme in peptidoglycan biosynthesis. The high degree of selectivity of the series for H. pylori makes these compounds attractive candidates for novel H. pylori-selective therapy.

MeSH terms

  • Amino Acid Isomerases / genetics
  • Amino Acid Isomerases / metabolism*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Enzyme Activation / drug effects
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / metabolism
  • Peptidoglycan / metabolism
  • Pyrimidines / chemistry*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Peptidoglycan
  • Pyrimidines
  • Amino Acid Isomerases
  • glutamate racemase