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Molecules. 2016 Jun 27;21(7). pii: E841. doi: 10.3390/molecules21070841.

Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents.

Author information

1
ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Faculty of Science and Engineering, Queensland University of Technology, Queensland 4001, Australia. a.verderosa@hdr.qut.edu.au.
2
Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. sarah@hancocklab.com.
3
Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cfuente@mit.edu.
4
Research Laboratory of Electronics, Department of Biological Engineering, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge 02139, MA, USA. cfuente@mit.edu.
5
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. cfuente@mit.edu.
6
Harvard Biophysics Program, Harvard University, Boston, MA 02115, USA. cfuente@mit.edu.
7
Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. bob@hancocklab.com.
8
ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Faculty of Science and Engineering, Queensland University of Technology, Queensland 4001, Australia. k.fairfull-smith@qut.edu.au.

Abstract

As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine linker achieved utilising reductive amination. The corresponding methoxyamine derivatives were prepared alongside their radical-containing counterparts as controls. Subsequent biological evaluation of the hybrid compounds on preformed P. aeruginosa flow cell biofilms divulged significant dispersal and eradication abilities for ciprofloxacin-nitroxide hybrid compound 10 (up to 95% eradication of mature biofilms at 40 μM). Importantly, these hybrids represent the first dual-action antimicrobial-nitroxide agents, which harness the dispersal properties of the nitroxide moiety to circumvent the well-known resistance of biofilms to treatment with antimicrobial agents.

KEYWORDS:

antibiotic; biofilm; ciprofloxacin; nitroxide; radical

PMID:
27355936
PMCID:
PMC6273952
DOI:
10.3390/molecules21070841
[Indexed for MEDLINE]
Free PMC Article

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