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Optical control of antibacterial activity

Nature Chemistry volume 5, pages 924928 (2013) | Download Citation

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Abstract

Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism. 

  • Compound C19H17N3O4

    (E)-1-Ethyl-7-((4-methoxyphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C20H19N3O4

    (E)-1-Ethyl-7-((4-methoxy-3-methylphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C21H21N3O4

    (E)-1-Ethyl-7-((4-methoxy-3,5-dimethylphenyl)-diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C22H23N3O4

    (E)-1-Ethyl-7-((4-methoxy-2,3,6-trimethylphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C20H19N3O4

    (E)-1-Ethyl-7-((2-methoxy-5-methylphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C19H16FN3O4

    (E)-1-Ethyl-7-((3-fluoro-4-methoxyphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C19H15F2N3O4

    (E)-7-((3,5-Difluoro-4-methoxyphenyl)diazenyl)-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C19H16FN3O4

    (E)-1-Ethyl-7-((5-fluoro-2-methoxyphenyl)diazenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

  • Compound C20H19N3O5

    (E)-7-((3,4-Dimethoxyphenyl)diazenyl)-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

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Acknowledgements

This work was supported financially by the Netherlands Organization for Scientific Research (NWO-CW), The Royal Netherlands Academy of Arts and Sciences (KNAW), the European Research Council (ERC; advanced grant no. 227897 to B.L.F.) and the Ministry of Education, Culture and Science (Gravity programme no. 024.001.035). The authors thank C. Poloni for help with the bacterial patterning experiments and W.R. Browne for discussions.

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Affiliations

  1. Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    • Willem A. Velema
    • , Mickel J. Hansen
    • , Wiktor Szymanski
    •  & Ben L. Feringa
  2. Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Nijenborgh 7, 9747 AG, Groningen, The Netherlands

    • Jan Pieter van der Berg
    •  & Arnold J. M. Driessen
  3. Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    • Arnold J. M. Driessen
    •  & Ben L. Feringa

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Contributions

B.L.F., W.A.V. and W.S. conceived the project and wrote the manuscript. W.A.V. designed the molecules. W.A.V. and M.J.H. performed the synthesis. W.A.V. and J.P.B. performed bacterial growth studies. B.L.F., W.S. and A.J.M.D. guided the research. All authors discussed the results and implications and commented on the manuscript at all stages.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ben L. Feringa.

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DOI

https://doi.org/10.1038/nchem.1750

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