Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3′-amino-[1,1′-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.

抗菌肽（AMPs）及其合成模拟物作为传统抗生素的新替代品，最近已引起人们的兴趣，试图克服许多微生物中抗生素耐药性的上升。AMP是大多数活生物体自然防御的一部分，它们还具有独特的抵抗细菌的作用机制。在此，通过结合3'-氨基-[1,1'-联苯] -3-羧酸骨架以模拟天然AMPs的基本特性，合成了一系列新的短两亲阳离子拟肽。通过改变疏水性和电荷，我们确定了对革兰氏阳性金黄色葡萄球菌（MIC = 15.6μM）和革兰氏阴性大肠杆菌均有效的最有效的类似物25g。（MIC = 7.8μM）细菌。细胞质渗透性测定结果显示25g主要通过细胞质膜中脂质的去极化作用。还研究了活性化合物对人细胞的细胞毒性，使用束缚的双层脂质膜（tBLM）溶解脂质双层及其对金黄色葡萄球菌和大肠杆菌已建立的生物膜的活性。