Limwongyut Jakkarin, Nie Chenyao, Moreland Alex S, Bazan Guillermo C
Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California Santa Barbara CA 93106 USA
Departments of Chemistry and Chemical Engineering, National University of Singapore 117543 Singapore
Chem Sci. 2020 Jul 24;11(31):8138-8144. doi: 10.1039/d0sc03679j.
A series of cationic conjugated oligoelectrolytes (COEs) was designed to understand how variations in molecular dimensions impact the relative activity against bacteria and mammalian cells. These COEs kept a consistent distyrylbenzene framework but differed in the length of linker between the core and the cationic site and the length of substitute on the quaternary ammonium functioned group. Their antimicrobial efficacy, mammalian cell cytotoxicity, hemolytic activity, and cell association were determined. We find that hydrophobicity is a factor that controls the degree of COE association to cells, but efficacy and cytotoxicity depend on more subtle structural features. was found to be the optimal structure with a minimum inhibitory concentration (MIC) of 4 μg mL against K12, low cytotoxicity against HepG2 cells and negligible hemolysis of red blood cells, even at 1024 μg mL. A time-kill kinetics study of against K12 demonstrates bactericidal activity. These findings provide the first systematic investigation of how COEs may be modulated to achieve low mammalian cell cytotoxicity with the long-range perspective of finding candidates suitable for developing a broad-spectrum antimicrobial agent.
设计了一系列阳离子共轭寡电解质（COE），以了解分子尺寸的变化如何影响其对细菌和哺乳动物细胞的相对活性。这些COE保持一致的二苯乙烯基苯骨架，但核心与阳离子位点之间的连接子长度以及季铵官能团上的取代基长度有所不同。测定了它们的抗菌功效、对哺乳动物细胞的细胞毒性、溶血活性和细胞结合情况。我们发现疏水性是控制COE与细胞结合程度的一个因素，但功效和细胞毒性取决于更细微的结构特征。已发现 是最佳结构，对K12的最低抑菌浓度（MIC）为4 μg/mL，对HepG2细胞的细胞毒性低，即使在1024 μg/mL时对红细胞的溶血作用也可忽略不计。对K12的时间-杀菌动力学研究表明 具有杀菌活性。这些发现首次系统研究了如何调节COE以实现低哺乳动物细胞毒性，从长远来看，旨在寻找适合开发广谱抗菌剂的候选物。
