期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 138, 期 -, 页码 590-601出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.06.058
关键词
Radical; Antibiotic; Biofilm; Nitroxide; Ciprofloxacin
资金
- Australian Research Council's Future Fellowship Scheme [FT140100746]
- Asian Office of Aerospace Research and Development [151OA087-154020]
- Queensland University of Technology
- Centre for Blood Research (CBR) graduate student award
- Gerhard Henrik Armauer-Hansen Memorial Scholarship
- Fundacion Ramon Areces (Spain)
- DTRA [HDTRA1-15-1-0050]
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 methoxy-amines 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 mu M. 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. Crown Copyright (C) 2017 Published by Elsevier Masson SAS. All rights reserved.
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