Design, synthesis, and biological evaluation of BODIPY-erythromycin probes for bacterial ribosomes

Bioorg Med Chem Lett. 2006 Feb 15;16(4):794-7. doi: 10.1016/j.bmcl.2005.11.028. Epub 2005 Nov 23.

Abstract

BODIPY-erythromycin probes of bacterial ribosomes were designed and synthesized by attaching a BODIPY fluorophore to the 4''- and 9-positions of the erythromycin structure. The probes exhibited excellent binding affinity to bacterial ribosomes and competed with erythromycin and other drugs whose binding sites are in the same vicinity of the 50S subunit. The synthetic fluorescent probe 5 was successfully adapted in our ultra high-throughput screening (uHTS) to identify novel ribosome inhibitors.

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Binding Sites
  • Binding, Competitive / drug effects
  • Boron Compounds* / chemical synthesis
  • Boron Compounds* / chemistry
  • Boron Compounds* / pharmacology
  • Drug Design
  • Erythromycin* / chemical synthesis
  • Erythromycin* / chemistry
  • Erythromycin* / pharmacology
  • Escherichia coli / chemistry
  • Escherichia coli / drug effects*
  • Escherichia coli / metabolism
  • Molecular Conformation
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry
  • Ribosomes / drug effects*
  • Ribosomes / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Anti-Bacterial Agents
  • Boron Compounds
  • Molecular Probes
  • Erythromycin