Structure-activity relationship in the oxazolidinone-quinolone hybrid series: influence of the central spacer on the antibacterial activity and the mode of action

Bioorg Med Chem Lett. 2003 Dec 1;13(23):4229-33. doi: 10.1016/j.bmcl.2003.07.028.

Abstract

Oxazolidinone-quinolone hybrids, which combine the pharmacophores of a quinolone and an oxazolidinone, were synthesised and shown to be active against a variety of susceptible and resistant Gram-positive and Gram-negative bacteria. The nature of the spacer greatly influences the antibacterial activity by directing the mode of action, that is quinolone- and/or oxazolidinone-like activity. The best compounds in this series have a balanced dual mode of action and overcome all types of resistance, including resistance to quinolones and linezolid, in clinically relevant Gram-positive pathogens.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / pharmacology
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / 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
  • DNA Topoisomerase IV
  • Linezolid