Naturally derived 3-aminoquinuclidine salts as new promising therapeutic agents.
3-substituted quinuclidine
Biological activity
Mode of antibacterial action
Quaternary ammonium salts
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
07
09
2024
accepted:
24
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Quaternary ammonium compounds (QACs) are a biologically active group of chemicals with a wide range of different applications. Due to their strong antibacterial properties and broad spectrum of activity, they are commonly used as ingredients in antiseptics and disinfectants. In recent years, the spread of bacterial resistance to QACs, exacerbated by the spread of infectious diseases, has seriously threatened public health and endangered human lives. Recent trends in this field have suggested the development of a new generation of QACs, in parallel with the study of bacterial resistance mechanisms. In this work, we present a new series of quaternary 3-substituted quinuclidine compounds that exhibit potent activity across clinically relevant bacterial strains. Most of the derivatives had minimal inhibitory concentrations (MICs) in the low single-digit micromolar range. Notably, QApCl and QApBr were selected for further investigation due to their strong antibacterial activity and low toxicity to human cells along with their minimal potential to induce bacterial resistance. These compounds were also able to inhibit the formation of bacterial biofilms more effectively than commercial standard, eradicating the bacterial population within just 15 min of treatment. The candidates employ a membranolytic mode of action, which, in combination with the generation of reactive oxygen species (ROS), destabilizes the bacterial membrane. This treatment results in a loss of cell volume and alterations in surface morphology, ultimately leading to bacterial cell death. The prominent antibacterial potential of quaternary 3-aminoquinuclidines, as exemplified by QApCl and QApBr, paves the way for new trends in the development of novel generation of QACs.
Identifiants
pubmed: 39482460
doi: 10.1038/s41598-024-77647-5
pii: 10.1038/s41598-024-77647-5
doi:
Substances chimiques
Anti-Bacterial Agents
0
Quinuclidines
0
Reactive Oxygen Species
0
Quaternary Ammonium Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26211Informations de copyright
© 2024. The Author(s).
Références
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