Synthesis and bioactivities of new N-terminal dipeptide mimetics with aromatic amide moiety: Broad-spectrum antibacterial activity and high antineoplastic activity
作者:Huan Li、Shuang Fu、Lijia Liu、Xuan Yuan、Yudan Wang、Chunhong Zhang、Hongxing Dong、Toshifumi Satoh
DOI:10.1016/j.ejmech.2021.113977
日期:2022.1
develop new antibacterial agents with broad-spectrum antibacterial activity and high selectivity. Here, a series of N-terminal dipeptide mimetics with an aromatic amide moiety were synthesized from amino acids. The effects of amino acid type and aromatic moiety on the biological activities of the mimetics were evaluated. The dipeptide mimetics not only showed significant broad-spectrum antibacterial activity
日益增长的耐多药细菌的流行正在成为严重的公共健康威胁。迫切需要开发具有广谱抗菌活性和高选择性的新型抗菌剂。在这里,从氨基酸合成了一系列具有芳香酰胺部分的N端二肽模拟物。评估了氨基酸类型和芳香部分对模拟物生物活性的影响。二肽模拟物不仅对革兰氏阴性菌(大肠杆菌和肺炎克雷伯菌)、革兰氏阳性菌(金黄色葡萄球菌)和耐药菌 MRSA(耐甲氧西林金黄色葡萄球菌)具有显着的广谱抗菌活性。) 但也证明了对金黄色葡萄球菌与哺乳动物红细胞的高选择性。L-缬氨酸与p的偶联产物-炔基苯胺(二肽模拟物7)表现出最好的抗菌活性,最低抑菌浓度(MIC)为2.5至5 μg/mL。此外,杀菌动力学和多代抗性试验表明,模拟物7既能快速杀死细菌,又具有较低的抗疟抗药性出现概率。同时,模拟物7具有抑制细菌生物膜形成和根除成熟生物膜的能力。细菌细胞膜的去极化和破坏是主要的杀菌机制,阻碍了细菌产生耐药性的倾向。此外,模拟物 7 对胃癌细胞也显示出良好的抗肿瘤活性