Synthesis and broad-spectrum biocidal effect of novel gemini quaternary ammonium compounds
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
39032408
DOI
10.1016/j.bioorg.2024.107646
PII: S0045-2068(24)00551-0
Knihovny.cz E-resources
- Keywords
- Disinfection, Octenidine, Quaternary ammonium salts, Resistance, Synthesis,
- MeSH
- Anti-Bacterial Agents * pharmacology chemical synthesis chemistry MeSH
- Antifungal Agents pharmacology chemical synthesis chemistry MeSH
- Antiviral Agents pharmacology chemical synthesis chemistry MeSH
- Bacteria drug effects MeSH
- Biofilms drug effects MeSH
- Fungi drug effects MeSH
- Imines MeSH
- Quaternary Ammonium Compounds * pharmacology chemical synthesis chemistry MeSH
- Humans MeSH
- Microbial Sensitivity Tests * MeSH
- Molecular Structure MeSH
- Mice MeSH
- Pyridinium Compounds pharmacology chemical synthesis chemistry MeSH
- Pyridines pharmacology chemistry chemical synthesis MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Antifungal Agents MeSH
- Antiviral Agents MeSH
- Imines MeSH
- Quaternary Ammonium Compounds * MeSH
- octenidine MeSH Browser
- Pyridinium Compounds MeSH
- Pyridines MeSH
Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G+ and G-) and their biofilms revealed that most compounds were highly effective against G+ bacteria, while compounds 7, 8, and 10-12 were effective against G- bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties.
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