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ABSTRACT We synthesized precision oligomers of thiophene with cationic and hydrophobic side chains to mimic the charge, hydrophobicity, and molecular size of antibacterial host defense peptides (HDPs). In this study, the source of cationic charge was a guanidinium salt moiety intended to reflect the structure of arginine-rich HDPs. Due to the pi-conjugated oligo(thiophene) backbone structure, these compounds absorb visible light in aqueous solution and react with dissolved oxygen to produce highly biocidal reactive oxygen species (ROS). Thus, the compounds exert bactericidal activity in the dark with dramatically enhanced potency upon visible light illumination. We find that guanylation of primary amine groups enhanced the activity of the oligomers in the dark but also mitigated their light-induced activity enhancement. In addition, we also quantified their toxicity to mammalian cell membranes using a hemolysis assay with red blood cells, in the light and dark conditions.
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Controlling Antimicrobial Activity of Quinolones Using Visible/NIR Light-Activated BODIPY Photocages
Controlling the activity of a pharmaceutical agent using light offers improved selectivity, reduction of adverse effects, and decreased environmental build-up. These benefits are especially attractive for antibiotics. Herein, we report a series of photoreleasable quinolones, which can be activated using visible/NIR light (520–800 nm). We have used BODIPY photocages with strong absorption in the visible to protect two different quinolone-based compounds and deactivate their antimicrobial properties. This activity could be recovered upon green or red light irradiation. A comprehensive computational study provides new insight into the reaction mechanism, revealing the relevance of considering explicit solvent molecules. The triplet excited state is populated and the photodissociation is assisted by the solvent. The light-controlled activity of these compounds has been assessed on a quinolone-susceptible E. coli strain. Up to a 32-fold change in the antimicrobial activity was measured.
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- Award ID(s):
- 1464956
- PAR ID:
- 10328676
- Date Published:
- Journal Name:
- Pharmaceutics
- Volume:
- 14
- Issue:
- 5
- ISSN:
- 1999-4923
- Page Range / eLocation ID:
- 1070
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/pharmaceutics14051070
