Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, Warsaw, 00-664, Poland.
Faculty of Chemical and Process Engineering, Warsaw University of Technology, Waryńskiego 1, Warsaw, 00-645, Poland.
Macromol Biosci. 2022 Jul;22(7):e2200094. doi: 10.1002/mabi.202200094. Epub 2022 May 18.
An alarming increase of antibiotic resistance among pathogens creates an urgent need to develop new antimicrobial agents. Many reported polycations show high antimicrobial activity along with low hemolytic activity. Unfortunately, most of those molecules remain highly cytotoxic against various mammalian cells. In this work, a systematic study on the impact of triethylene glycol monomethyl ether side groups (short polyethylene glycol (PEG) analog) on antimicrobial, hemolytic, and cytotoxic properties of novel amphiphilic ionenes is presented. A detailed description of synthesis, leading to well-defined alternating polymers, which differ in structural elements responsible for hydrophilicity (PEG) and hydrophobicity (alkyl chain), is presented. Obtained results show that the PEG moiety and fine-tuned hydrophilic-lipophilic balance of ionenes synergistically lead to low cytotoxic, low hemolytic molecules with high activity against S. aureus, including methicillin-resistant strains (MRSA). Additionally, the results of mechanistic studies on bacterial cells and fluorescently labeled liposomes are also discussed.
病原体对抗生素耐药性的惊人增长，迫切需要开发新的抗菌药物。许多已报道的聚阳离子具有很高的抗菌活性和低溶血活性。不幸的是，大多数这些分子对各种哺乳动物细胞仍具有高度细胞毒性。在这项工作中，我们系统地研究了三甘醇单甲醚侧基（短聚乙二醇（PEG）类似物）对新型两亲性离子聚合物的抗菌、溶血和细胞毒性的影响。详细描述了合成过程，得到了结构明确的交替聚合物，这些聚合物在亲水（PEG）和疏水性（烷基链）的结构单元上有所不同。研究结果表明，PEG 部分和离子聚合物的精细亲水-亲脂平衡协同作用，导致对金黄色葡萄球菌（包括耐甲氧西林金黄色葡萄球菌（MRSA））具有高活性、低细胞毒性、低溶血的分子。此外，还讨论了对细菌细胞和荧光标记脂质体的机制研究结果。
