Double BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC)
Double BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC)
复制标题
双 BAC 和三 BAC：苯扎氯铵 (BAC) 多阳离子衍生物消毒性能的系统分析
DOI：
10.1002/cmdc.202300018
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发表时间：
2023
期刊：
影响因子：
3.4
通讯作者：
Minbiole, Kevin P. C.
中科院分区：
文献类型：
--
作者：
Toles, Zachary E. A.;Wu, Alice;Sanchez, Christian A.;Michaud, Marina E.;Thierer, Laura M.;Wuest, William M.;Minbiole, Kevin P. C.
在过去的几十年里，现有的季铵盐类消毒剂的缺点越来越明显。虽然苯扎氯铵(BAC)通过外科准备、家庭使用和工业应用已有近一个世纪的显著保护人类健康的作用，但细菌耐药性的增加使其有效性下降。鉴于最近的一些工作告诉我们，多阳离子两亲性消毒剂显示出更高的活性以及减少对耐药性的敏感性，我们着手制备27个 多阳离子QAC，试图清楚地记录下一代生物碱结构的结构-活性关系。精选的双阳离子BAC衍生物对所有测试的七种细菌表现出一位数的微摩尔活性，MIC值为BAC的2-32倍。尤其值得注意的是，对鲍曼不动杆菌和铜绿假单胞菌等更令人担忧的细菌的改进，这些细菌对BAC等传统消毒剂构成了现代威胁。由于合成路线简单，产率始终较高(平均∼为80 %)，生物活性强，具有明显的合成趋势和较强的治疗指数。
Over the past decades, the shortcomings of established quaternary ammonium disinfectants have become increasingly clear. Although benzalkonium chloride (BAC) has enjoyed nearly a century of significantly protecting human health through surgical preparation, home use, and industrial applications, increasing levels of bacterial resistance have rendered it decreasingly effective. In light of more recent efforts that have informed us that multicationic amphiphilic disinfectants show both higher activity as well as diminished susceptibility to resistance, we embarked on the preparation of 27 multicationic QACs in an attempt to clearly document structure‐activity relationships of next‐generation BAC structures. Select biscationic BAC derivatives demonstrate single‐digit micromolar activity against all seven bacteria tested and MIC values of 2‐ to 32‐fold better than BAC. Particularly notable is the improvement against the more concerning bacteria likeAcinetobacter baumanniiandPseudomonas aeruginosa, which pose a modern threat to legacy disinfectants like BAC. With simple synthetic paths, consistently high yields (averaging ∼80 %), and strong biological activity, potent structures with clear SAR trends and strong therapeutic indices have been established.