DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: synthesis and antibacterial activity

Bioorg Med Chem Lett. 2009 Feb 1;19(3):894-9. doi: 10.1016/j.bmcl.2008.11.102. Epub 2008 Dec 3.

Abstract

The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / chemistry
  • Anti-Infective Agents / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • DNA Topoisomerase IV / antagonists & inhibitors*
  • Drug Design
  • Enterococcus faecalis / metabolism
  • Escherichia coli / metabolism
  • Gram-Positive Bacteria / metabolism
  • Humans
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • Pyridines / chemistry
  • Staphylococcus aureus / metabolism
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*
  • Triazoles / chemistry

Substances

  • Anti-Infective Agents
  • Imidazoles
  • Pyridines
  • Topoisomerase II Inhibitors
  • Triazoles
  • Adenosine Triphosphatases
  • DNA Topoisomerase IV