| Autor: |
Jessica E. Boles, Charlotte Bennett, Jennifer Baker, Kira L. F. Hilton, Hiral A. Kotak, Ewan R. Clark, Yifan Long, Lisa J. White, Hin Yuk Lai, Charlotte K. Hind, J. Mark Sutton, Michelle D. Garrett, Anne Cheasty, Jose L. Ortega-Roldan, Mark Charles, Cally J. E. Haynes, Jennifer R. Hiscock |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| ISSN: |
2041-6520 |
| Popis: |
The rise of antimicrobial resistance remains one of the greatest global health threats facing humanity. Furthermore, the development of novel antibiotics has all but ground to a halt due to a collision of intersectional pressures. Herein we determine the antimicrobial efficacy for 14 structurally related supramolecular self-associating amphiphiles against clinically relevant Gram-positive methicillin resistant Staphylococcus aureus and Gram-negative Escherichia coli. We establish the ability of these agents to selectively target phospholipid membranes of differing compositions, through a combination of computational host:guest complex formation simulations, synthetic vesicle lysis, adhesion and membrane fluidity experiments, alongside our novel 1H NMR CPMG nanodisc coordination assays, to verify a potential mode of action for this class of compounds and enable the production of evermore effective next-generation antimicrobial agents. Finally, we select a 7-compound subset, showing two lead compounds to exhibit ‘druggable’ profiles through completion of a variety of in vivo and in vitro DMPK studies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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