Tuning riboflavin derivatives for photodynamic inactivation of pathogens.
Authors
Crocker, Leander B
Lee, Ju Hyun
Mital, Suraj
Mills, Gabrielle C
Schack, Sina
Bistrović-Popov, Andrea
Franck, Christoph O
Kaminski, Clemens F
Christie, Graham
Publication Date
2022-04-21Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Crocker, L. B., Lee, J. H., Mital, S., Mills, G. C., Schack, S., Bistrović-Popov, A., Franck, C. O., et al. (2022). Tuning riboflavin derivatives for photodynamic inactivation of pathogens.. Sci Rep, 12 (1) https://doi.org/10.1038/s41598-022-10394-7
Abstract
The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.
Keywords
Article, /639/638/549, /639/638/439, /692/699/255/1318, /692/699/255/2514, article
Sponsorship
Engineering and Physical Sciences Research Council (EP/H018301/1)
Engineering and Physical Sciences Research Council (EP/L015889/1)
Engineering and Physical Sciences Research Council (EP/S009000/1)
EPSRC (via University of Birmingham) (EP/V029762/1)
Identifiers
s41598-022-10394-7, 10394
External DOI: https://doi.org/10.1038/s41598-022-10394-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336316
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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