Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland.
Department of Histology, Faculty of Medicine, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
Int J Mol Sci. 2021 Mar 24;22(7):3299. doi: 10.3390/ijms22073299.
Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic -terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. l-cystine diamide and l-lysine amide linkers were used as spacers. Antimicrobial activity against planktonic and biofilm cultures of ESKAPE (, , , , , and spp.) strains and sp. as well as hemolytic and cytotoxic activities were examined. Moreover, antimicrobial activity in the presence of human serum and the ability to form micelles were evaluated. Membrane permeabilization study, serum stability assay, and molecular dynamics were performed. Generally, critical aggregation concentration was linearly correlated with hydrophobicity. Gemini surfactants were more active than the parent USCLs, and they turned out to be selective antimicrobial agents with relatively low hemolytic and cytotoxic activities. Geminis with the l-cystine diamide spacer seem to be less cytotoxic than their l-lysine amide counterparts, but they exhibited lower antibiofilm and antimicrobial activities in serum. In some cases, geminis with branched fatty acid chains and -terminal hydrophobic amino acid resides exhibited enhanced selectivity to pathogens over human cells.
超短阳离子脂肽（USCLs）和双子阳离子表面活性剂是一类强效的抗菌剂。我们最近的研究表明，在 USCLs 中通过分支和缩短脂肪酸链，并同时添加疏水性末端氨基酸，可以得到具有增强选择性的化合物。在这里，我们将这种方法引入到富含精氨酸的双子阳离子表面活性剂中。使用 l-胱氨酸二酰胺和 l-赖氨酸酰胺作为连接体作为间隔基。检测了这些化合物对 ESKAPE（,,,,, 和 spp.）菌株和 sp. 的浮游生物和生物膜培养物以及溶血和细胞毒性的抗菌活性。此外，还评估了在人血清存在下的抗菌活性和形成胶束的能力。进行了膜通透性研究、血清稳定性测定和分子动力学研究。通常，临界聚集浓度与疏水性呈线性相关。双子表面活性剂比母体 USCLs 更具活性，并且它们是具有相对较低溶血和细胞毒性的选择性抗菌剂。与 l-赖氨酸酰胺相比，具有 l-胱氨酸二酰胺间隔基的双子似乎对细胞的细胞毒性较低，但在血清中它们的抗生物膜和抗菌活性较低。在某些情况下，具有分支脂肪酸链和末端疏水性氨基酸残基的双子表现出对病原体相对于人类细胞的增强选择性。
