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Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents Verderosa, Anthony D.; Mansour, Sarah C.; De la Fuente-Núñez, César; Hancock, R. E. W. (Robert E. W.); Fairfull-Smith, Kathryn E.

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.

Item Metadata

Title
Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents
Creator
Verderosa, Anthony D.; Mansour, Sarah C.; De la Fuente-Núñez, César; Hancock, R. E. W. (Robert E. W.); Fairfull-Smith, Kathryn E.
Contributor
University of British Columbia. Centre for Microbial Diseases and Immunity Research
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2016-06-27
Description
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.
Subject
Radical; Antibiotic; Biofilm; Nitroxide; Ciprofloxacin
Genre
Article
Type
Text
Language
eng
Date Available
2019-05-27
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0379018
URI
http://hdl.handle.net/2429/70338
Affiliation
Science, Faculty of; Other UBC; Non UBC; Microbiology and Immunology, Department of
Citation
Molecules 21 (7): 841 (2016)
Publisher DOI
10.3390/molecules21070841
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0