Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, P. R. China.
East China University of Science and Technology, Shanghai 200237, P. R. China.
ACS Appl Bio Mater. 2024 Nov 18;7(11):7444-7452. doi: 10.1021/acsabm.4c01056. Epub 2024 Oct 30.
Multidrug-resistant (MDR) Gram-negative bacteria infections have gradually become a more serious health problem recently, and antibacterial drugs are urgently needed to tackle MDR Gram-negative bacteria. Herein, we synthesized a series of quaternary ammonium salt derivatives of hyperbranched polylysine (HPL--) with different alkyl chain lengths ( = 4, 8, 12, 16) and grafting ratios ( = 5.8-21.0) of alkyl quaternary ammonium salts (). HPL--s exhibited excellent antibacterial activities against drug-sensitive and , and specifically, HPL-C12-s were also highly active against MDR and . The cytotoxicity and hemolytic activity of HPL--s increased with the increase in the alkyl chain length and the grafting ratio of . The killing study proved that HPL-C12-9.5 had fast killing kinetics and was bactericidal toward both drug-sensitive and MDR . The mechanistic studies showed that, similar to hyperbranched polylysine (HPL), HPL-C12-9.5 killed bacteria by disrupting the cell membranes and causing leakage of the cytoplasmic contents. HPL-C12-s might have potential as an antibacterial agent to combat MDR Gram-negative bacteria.
多药耐药（MDR）革兰氏阴性菌感染最近逐渐成为一个更严重的健康问题，急需抗菌药物来应对 MDR 革兰氏阴性菌。在此，我们合成了一系列具有不同烷基链长度（ = 4、8、12、16）和支化多聚赖氨酸（HPL--）上季铵盐接枝率（ = 5.8-21.0）的季铵盐衍生物（）。HPL--对药敏和 具有优异的抗菌活性，特别是 HPL-C12-s 对 MDR 和 也具有很高的活性。HPL--的细胞毒性和溶血活性随烷基链长度和 的接枝率的增加而增加。杀菌研究证明，HPL-C12-9.5 具有快速的杀菌动力学，对药敏和 MDR 均具有杀菌作用。机制研究表明，与支化多聚赖氨酸（HPL）类似，HPL-C12-9.5 通过破坏细胞膜并导致细胞质内容物泄漏来杀死细菌。HPL-C12-s 可能具有作为抗 MDR 革兰氏阴性菌的抗菌剂的潜力。
