An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants

Bioorg Med Chem. 2014 Aug 15;22(16):4490-8. doi: 10.1016/j.bmc.2014.05.054. Epub 2014 Jun 14.

Abstract

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy.

Keywords: Antibiotics; Bacteria; Click chemistry; Fluorescent probes; Linezolid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Azides / chemistry
  • Azides / pharmacology*
  • Click Chemistry
  • Drug Design
  • Fluorescent Dyes / analysis*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • Gram-Positive Bacteria / cytology*
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / isolation & purification
  • Microbial Sensitivity Tests
  • Microscopy, Confocal
  • Models, Molecular
  • Molecular Structure
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Azides
  • Fluorescent Dyes
  • Oxazolidinones