Ester- and amide-containing multiQACs: Exploring multicationic soft antimicrobial agents

被引：39

作者：

Allen, Ryan A. ^{[1
]}

Jennings, Megan C. ^{[2
]}

Mitchell, Myles A. ^{[1
]}

Al-Khalifa, Saleh E. ^{[1
]}

Wuest, William M. ^{[2
]}

Minbiole, Kevin P. C. ^{[1
]}

机构：

[1] Villanova Univ, Dept Chem, Villanova, PA 19085 USA

[2] Temple Univ, Dept Chem, Philadelphia, PA 19122 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 10期

基金：

美国国家科学基金会;

关键词：

Antiseptics; Methicillin-resistant Staphylococcus aureus (MRSA); Quaternary ammonium compounds; Soft antimicrobials; QUATERNARY AMMONIUM DISINFECTANTS; BENZALKONIUM CHLORIDE; LIQUID-CHROMATOGRAPHY; ANTIBACTERIAL AGENTS; BACTERICIDAL ACTION; AMPHIPHILES; SALTS; CONSTITUTION; DEGRADATION; SURFACTANTS;

D O I：

10.1016/j.bmcl.2017.03.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 similar to 1 mu M. 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. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：2107 / 2112

页数：6

共 41 条

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