Novel quinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV

Bioorg Med Chem Lett. 2013 May 15;23(10):2955-61. doi: 10.1016/j.bmcl.2013.03.047. Epub 2013 Mar 21.

Abstract

A structurally novel set of inhibitors of bacterial type II topoisomerases with potent in vitro and in vivo antibacterial activity was developed. Dual-targeting ability, hERG inhibition, and pharmacokinetic properties were also assessed.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • DNA Gyrase / metabolism
  • DNA Topoisomerase IV / antagonists & inhibitors*
  • DNA Topoisomerase IV / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinolines / administration & dosage
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / enzymology
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Ether-A-Go-Go Potassium Channels
  • Quinolines
  • Topoisomerase II Inhibitors
  • quinoline
  • DNA Topoisomerase IV
  • DNA Gyrase
  • DNA Topoisomerases, Type II