Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles.

Autor: Forman ME; Department of Chemistry, Villanova University, 800 East Lancaster Avenue, Villanova, PA, 19085, USA., Jennings MC; Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, PA, 19122, USA., Wuest WM; Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, PA, 19122, USA. wwuest@temple.edu., Minbiole KP; Department of Chemistry, Villanova University, 800 East Lancaster Avenue, Villanova, PA, 19085, USA. kevin.minbiole@villanova.edu.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2016 Jul 05; Vol. 11 (13), pp. 1401-5. Date of Electronic Publication: 2016 Jun 01.
DOI: 10.1002/cmdc.201600176
Abstrakt: 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 25 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.
(© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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