Ciprofloxacin-nitroxide hybrids with potential for biofilm control

Anthony D. Verderosa, César de la Fuente-Núñez, Sarah C. Mansour, Jicong Cao, Timothy K. Lu, Robert E.W. Hancock, Kathryn E. Fairfull-Smith

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

As bacterial biofilms display extreme tolerance to conventional antibiotic treatments, it has become imperative to develop new antibacterial strategies with alternative mechanisms of action. Herein, we report the synthesis of a series of ciprofloxacin-nitroxide conjugates and their corresponding methoxyamine derivatives in high yield. This was achieved by linking various nitroxides or methoxyamines to the secondary amine of the piperazine ring of ciprofloxacin using amide bond coupling. Biological evaluation of the prepared compounds on preformed P. aeruginosa biofilms in flow cells revealed substantial dispersal with ciprofloxacin-nitroxide hybrid 25, and virtually complete killing and removal (94%) of established biofilms in the presence of ciprofloxacin-nitroxide hybrid 27. Compounds 25–28 were shown to be non-toxic in both human embryonic kidney 293 (HEK 293) cells and human muscle rhabdomyosarcoma (RD) cells at concentrations up to 40 μM. Significantly, these hybrids demonstrate the potential of antimicrobial-nitroxide agents to overcome the resistance of biofilms to antimicrobials via stimulation of biofilm dispersal or through direct cell killing.

Original languageEnglish
Pages (from-to)590-601
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume138
DOIs
Publication statusPublished or Issued - 2017

Keywords

  • Antibiotic
  • Biofilm
  • Ciprofloxacin
  • Nitroxide
  • Radical

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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