Ester- and amide-containing multiQACs: Exploring multicationic soft antimicrobial agents
| Autor: | Ryan A. Allen, Megan C. Jennings, Kevin P. C. Minbiole, Myles A. Mitchell, William M. Wuest, Saleh Alkhalifa |
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| Rok vydání: | 2017 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Lysis medicine.drug_class Gram-positive bacteria Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Gram-Positive Bacteria 010402 general chemistry Hemolysis 01 natural sciences Biochemistry Hydrolysis chemistry.chemical_compound Anti-Infective Agents Antiseptic Amide Gram-Negative Bacteria Drug Discovery medicine Organic chemistry Molecular Biology biology 010405 organic chemistry Chemistry Organic Chemistry Esters biology.organism_classification Antimicrobial Amides 0104 chemical sciences Quaternary Ammonium Compounds Molecular Medicine Chemical stability Antibacterial activity Disinfectants |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 27:2107-2112 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2017.03.077 |
| Popis: | Quaternary ammonium compounds (QACs) are ubiquitous antiseptics whose chemical stability is both an aid to prolonged antibacterial activity and a liability to the environment. Soft antimicrobials, such as QACs designed to decompose in relatively short times, show the promise to kill bacteria effectively but not leave a lasting footprint. We have designed and prepared 40 soft QAC compounds based on both ester and amide linkages, in a systematic study of mono-, bis-, and tris-cationic QAC species. Antimicrobial activity, red blood cell lysis, and chemical stability were assessed. Antiseptic activity was strong against a panel of six bacteria including two MRSA strains, with low micromolar activity seen in many compounds; amide analogs showed superior activity over ester analogs, with one bisQAC displaying average MIC activity of ∼1μM. For a small subset of highly bioactive compounds, hydrolysis rates in pure water as well as buffers of pH =4, 7, and 10 were tracked by LCMS, and indicated good stability for amides while rapid hydrolysis was observed for all compounds in acidic conditions. |
| Databáze: | OpenAIRE |
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