Novel oxazolidinone-quinolone hybrid antimicrobials

Bioorg Med Chem Lett. 2003 Dec 1;13(23):4213-6. doi: 10.1016/j.bmcl.2003.07.021.

Abstract

Antimicrobial compounds incorporating oxazolidinone and quinolone pharmacophore substructures have been synthesized and evaluated. Representative analogues 2, 5, and 6 display an improved potency versus linezolid against gram-positive and fastidious gram-negative pathogens. The compounds are also active against linezolid- and ciprofloxacin-resistant Staphylococcus aureus and Enterococcus faecium strains. The MOA for these new antimicrobials is consistent with a combination of protein synthesis and gyrase A/topoisomerase IV inhibition, with a structure-dependent degree of the contribution from each inhibitory mechanism.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / pharmacology
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Ciprofloxacin / pharmacology
  • DNA Topoisomerase IV / antagonists & inhibitors
  • Drug Resistance, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Linezolid
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology*
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Quinolones
  • Ciprofloxacin
  • DNA Topoisomerase IV
  • Linezolid