Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles.
ChemMedChem
; 11(13): 1401-5, 2016 07 05.
Article
em En
| MEDLINE
| ID: mdl-27245743
ABSTRACT
Bacteria contaminate surfaces in a wide variety of environments, causing severe problems across a number of industries. In a continuation of our campaign to develop novel antibacterial quaternary ammonium compounds (QACs) as useful antiseptics, we have identified a starting material bearing four tertiary amines, enabling the rapid synthesis of several tris- and tetracationic QACs. Herein we report the synthesis and biological activity of a series of 24 multiQACs deemed the "superT" family, and an investigation of the role of cationic charge in antimicrobial and anti-biofilm activity, as well as toxicity. This class represents the most potent series of QACs reported to date against methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) and minimum biofilm eradication concentrations (MBECs) as low as 0.25 and 25â
µm, respectively. Based on the significant cell-surface-charge differences between bacterial and eukaryotic cells, in certain cases we observed excellent efficacy-to-toxicity profiles, exceeding a 100-fold differential. This work further elucidates the chemical underpinnings of disinfectant efficacy versus toxicity based on cationic charge.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tensoativos
/
Compostos de Amônio Quaternário
/
Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos