Thirteen cationic peptidomimetics derived from amino acids bearing an alkyl or ethynylphenyl moiety that mimic the structure of cationic antibacterial peptides were designed and synthesized using a simple coupling reaction of an amino acid with a substituted amine. Antibacterial activities of the resulting peptidomimetics against drug-sensitive bacteria, such as Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis, Gram-negative Escherichia coli (E. coli) and Salmonella enterica, and a drug-resistant bacterium, methicillin-resistant S. aureus (MRSA), were systematically evaluated. Most peptidomimetics show significant broad-spectrum antibacterial activity. A-L-Iso-C₁₂ (isoleucine derivative bearing a dodecyl moiety) show MICs of 2.5 μg/mL against S. aureus and 4 μg/mL against MRSA and A-L-Val-C₁₂ (valine derivative bearing a dodecyl moiety) show MICs of 1.67 μg/mL against E. coli and 8.3 μg/mL against MRSA. A-L-Val-C₁₂ showed low cytotoxicity toward L929 cells in comparison with SGC 7901 cells, indicating tumor-directed killing by peptidomimetics while avoiding toxicity to normal cells. The influences of type of amino acid and substituent, length of substituent, and stereochemistry of amino acids on antibacterial activity and cytotoxicity of peptidomimetics were systematically investigated. The results indicate that this series of cationic peptidomimetics derived from amino acids display antitumor activity and may be useful for treatment of bacterial infections.

使用氨基酸与取代胺的简单偶联反应，设计并合成了 13 种源自带有烷基或乙炔基苯基部分的氨基酸的阳离子肽模拟物，模拟阳离子抗菌肽的结构。所得肽模拟物对药物敏感细菌的抗菌活性，例如革兰氏阳性葡萄球菌（金黄色葡萄球菌）和枯草芽孢杆菌、革兰氏阴性大肠杆菌（大肠杆菌）和肠沙门氏菌，以及耐药菌甲氧西林抗性金黄色葡萄球菌(MRSA)，进行了系统评估。大多数肽模拟物显示出显着的广谱抗菌活性。AL-Iso-C ₁₂（带有十二烷基部分的异亮氨酸衍生物）对金黄色葡萄球菌的MIC 为 2.5 μg/mL，对 MRSA 的MIC 为4 μg/mL，AL-Val-C ₁₂（带有十二烷基部分的缬氨酸衍生物）对金黄色葡萄球菌的MIC 为1.67 μg/mL 抗大肠杆菌，8.3 μg/mL 抗 MRSA。AL-Val-C ₁₂与 SGC 7901 细胞相比，对 L929 细胞显示出较低的细胞毒性，表明肽模拟物对肿瘤进行了杀伤，同时避免了对正常细胞的毒性。系统研究了氨基酸类型和取代基、取代基长度和氨基酸立体化学对肽模拟物抗菌活性和细胞毒性的影响。结果表明，这一系列源自氨基酸的阳离子肽模拟物显示出抗肿瘤活性，可用于治疗细菌感染。