Schallenhammer Stephanie A, Duggan Stephanie M, Morrison Kelly R, Bentley Brian S, Wuest William M, Minbiole Kevin P C
Department of Chemistry, Villanova University, Villanova, PA 19085, USA.
Department of Chemistry, Emory University, Atlanta, GA, 30322, USA.
ChemMedChem. 2017 Dec 7;12(23):1931-1934. doi: 10.1002/cmdc.201700597. Epub 2017 Nov 14.
Benzalkonium chloride (BAC) and cetyl pyridinium chloride (CPC) are two of the most common household antiseptics, but show weaker efficacy against Gram-negative bacteria as well as against methicillin-resistant Staphylococcus aureus (MRSA) strains, relative to other S. aureus strains. We prepared 28 novel quaternary ammonium compounds (QACs) that represent a hybrid of these two structures, using 1- to 2-step synthetic sequences. The biscationic (bisQAC) species prepared show uniformly potent activity against six bacterial strains tested, with nine novel antiseptics displaying single-digit micromolar activity across the board. Effects of unequal chain lengths of two installed side chains had less impact than the overall number of side chain carbon atoms present, which was optimal at 22-25 carbons. This is further indication that simple refinements to multiQAC architectures can show improvement over current household antiseptics.
苯扎氯铵（BAC）和西吡氯铵（CPC）是两种最常见的家用防腐剂，但相对于其他金黄色葡萄球菌菌株，它们对革兰氏阴性菌以及耐甲氧西林金黄色葡萄球菌（MRSA）菌株的杀菌效果较弱。我们采用1至2步合成序列，制备了28种新型季铵化合物（QAC），它们是这两种结构的杂合体。所制备的双阳离子（bisQAC）化合物对测试的六种细菌菌株均表现出一致的强效活性，其中九种新型防腐剂对所有菌株的活性均在个位数微摩尔范围内。两条侧链长度不等的影响小于侧链碳原子的总数，侧链碳原子总数为22至25个时效果最佳。这进一步表明，对多QAC结构进行简单优化可以比目前的家用防腐剂表现更优。
