Scaffold-Hopping of Multicationic Amphiphiles Yields Three New Classes of Antimicrobials
| Autor: | Anthony A. Iannetta, William M. Wuest, Megan C. Jennings, Madison H. Fletcher, Kevin P. C. Minbiole, Myles A. Mitchell |
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| Rok vydání: | 2015 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Gram-negative bacteria Microbial Sensitivity Tests medicine.disease_cause Gram-Positive Bacteria Biochemistry Minimum inhibitory concentration Anti-Infective Agents Cations Amphiphile Gram-Negative Bacteria medicine Molecular Biology Alkyl chemistry.chemical_classification biology Organic Chemistry Biofilm biology.organism_classification Antimicrobial Methicillin-resistant Staphylococcus aureus Combinatorial chemistry Quaternary Ammonium Compounds chemistry Staphylococcus aureus Biofilms Molecular Medicine |
| Zdroj: | Chembiochem : a European journal of chemical biology. 16(16) |
| ISSN: | 1439-7633 |
| Popis: | Quaternary ammonium compounds (QACs) are a vital class of antiseptics. Recent investigations into their construction are uncovering novel and potent multicationic variants. Based on a trisQAC precedent, we have implemented a scaffold-hopping approach to develop alternative QAC architectures that display 1-3 long alkyl chains in specific projections from cyclic and branched core structures bearing 3-4 nitrogen atoms. The preparation of 30 QAC structures allowed for correlation of scaffold structure with antimicrobial activity. We identified QACs with limited conformational flexibility that have improved bioactivity against planktonic bacteria as compared to their linear counterparts. We also confirmed that resistance, as evidenced by an increased minimum inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus (MRSA) compared to methicillin-susceptible Staphylococcus aureus (MSSA), can reduce efficacy up to 64-fold for monocationic QACs. Differentiation of antimicrobial and anti-biofilm activity, however, was not observed, suggesting that these compounds utilize a non-specific mode of eradication. |
| Databáze: | OpenAIRE |
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