Cargando…
Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation
[Image: see text] The field of photopharmacology aims to introduce smart drugs that, through the incorporation of molecular photoswitches, allow for the remote spatial and temporal control of bioactivity by light. This concept could be particularly beneficial in the treatment of bacterial infections...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2017
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730949/ https://www.ncbi.nlm.nih.gov/pubmed/29136373 http://dx.doi.org/10.1021/jacs.7b09281 |
_version_ | 1783286438534578176 |
---|---|
author | Wegener, Michael Hansen, Mickel J. Driessen, Arnold J. M. Szymanski, Wiktor Feringa, Ben L. |
author_facet | Wegener, Michael Hansen, Mickel J. Driessen, Arnold J. M. Szymanski, Wiktor Feringa, Ben L. |
author_sort | Wegener, Michael |
collection | PubMed |
description | [Image: see text] The field of photopharmacology aims to introduce smart drugs that, through the incorporation of molecular photoswitches, allow for the remote spatial and temporal control of bioactivity by light. This concept could be particularly beneficial in the treatment of bacterial infections, by reducing the systemic and environmental side effects of antibiotics. A major concern in the realization of such light-responsive drugs is the wavelength of the light that is applied. Studies on the photocontrol of biologically active agents mostly rely on UV light, which is cytotoxic and poorly suited for tissue penetration. In our efforts to develop photoswitchable antibiotics, we introduce here antibacterial agents whose activity can be controlled by visible light, while getting into the therapeutic window. For that purpose, a UV-light-responsive core structure based on diaminopyrimidines with suitable antibacterial properties was identified. Subsequent modification of an azobenzene photoswitch moiety led to structures that allowed us to control their activity against Escherichia coli in both directions with light in the visible region. For the first time, full in situ photocontrol of antibacterial activity in the presence of bacteria was attained with green and violet light. Most remarkably, one of the diaminopyrimidines revealed an at least 8-fold difference in activity before and after irradiation with red light at 652 nm, showcasing the effective “activation” of a biological agent otherwise inactive within the investigated concentration range, and doing so with red light in the therapeutic window. |
format | Online Article Text |
id | pubmed-5730949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-57309492017-12-17 Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation Wegener, Michael Hansen, Mickel J. Driessen, Arnold J. M. Szymanski, Wiktor Feringa, Ben L. J Am Chem Soc [Image: see text] The field of photopharmacology aims to introduce smart drugs that, through the incorporation of molecular photoswitches, allow for the remote spatial and temporal control of bioactivity by light. This concept could be particularly beneficial in the treatment of bacterial infections, by reducing the systemic and environmental side effects of antibiotics. A major concern in the realization of such light-responsive drugs is the wavelength of the light that is applied. Studies on the photocontrol of biologically active agents mostly rely on UV light, which is cytotoxic and poorly suited for tissue penetration. In our efforts to develop photoswitchable antibiotics, we introduce here antibacterial agents whose activity can be controlled by visible light, while getting into the therapeutic window. For that purpose, a UV-light-responsive core structure based on diaminopyrimidines with suitable antibacterial properties was identified. Subsequent modification of an azobenzene photoswitch moiety led to structures that allowed us to control their activity against Escherichia coli in both directions with light in the visible region. For the first time, full in situ photocontrol of antibacterial activity in the presence of bacteria was attained with green and violet light. Most remarkably, one of the diaminopyrimidines revealed an at least 8-fold difference in activity before and after irradiation with red light at 652 nm, showcasing the effective “activation” of a biological agent otherwise inactive within the investigated concentration range, and doing so with red light in the therapeutic window. American Chemical Society 2017-11-14 2017-12-13 /pmc/articles/PMC5730949/ /pubmed/29136373 http://dx.doi.org/10.1021/jacs.7b09281 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Wegener, Michael Hansen, Mickel J. Driessen, Arnold J. M. Szymanski, Wiktor Feringa, Ben L. Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation |
title | Photocontrol
of Antibacterial Activity: Shifting from
UV to Red Light Activation |
title_full | Photocontrol
of Antibacterial Activity: Shifting from
UV to Red Light Activation |
title_fullStr | Photocontrol
of Antibacterial Activity: Shifting from
UV to Red Light Activation |
title_full_unstemmed | Photocontrol
of Antibacterial Activity: Shifting from
UV to Red Light Activation |
title_short | Photocontrol
of Antibacterial Activity: Shifting from
UV to Red Light Activation |
title_sort | photocontrol
of antibacterial activity: shifting from
uv to red light activation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730949/ https://www.ncbi.nlm.nih.gov/pubmed/29136373 http://dx.doi.org/10.1021/jacs.7b09281 |
work_keys_str_mv | AT wegenermichael photocontrolofantibacterialactivityshiftingfromuvtoredlightactivation AT hansenmickelj photocontrolofantibacterialactivityshiftingfromuvtoredlightactivation AT driessenarnoldjm photocontrolofantibacterialactivityshiftingfromuvtoredlightactivation AT szymanskiwiktor photocontrolofantibacterialactivityshiftingfromuvtoredlightactivation AT feringabenl photocontrolofantibacterialactivityshiftingfromuvtoredlightactivation |