Berkov-Zrihen Yifat, Herzog Ido M, Benhamou Raphael I, Feldman Mark, Steinbuch Kfir B, Shaul Pazit, Lerer Shachar, Eldar Avigdor, Fridman Micha
School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801 (Israel).
Chemistry. 2015 Mar 9;21(11):4340-9. doi: 10.1002/chem.201406404. Epub 2015 Feb 4.
Antimicrobial cationic amphiphiles derived from aminoglycoside pseudo-oligosaccharide antibiotics interfere with the structure and function of bacterial membranes and offer a promising direction for the development of novel antibiotics. Herein, we report the design and synthesis of cationic amphiphiles derived from the pseudo-trisaccharide aminoglycoside tobramycin and its pseudo-disaccharide segment nebramine. Antimicrobial activity, membrane selectivity, mode of action, and structure-activity relationships were studied. Several cationic amphiphiles showed marked antimicrobial activity, and one amphiphilic nebramine derivative proved effective against all of the tested strains of bacteria; furthermore, against several of the tested strains, this compound was well over an order of magnitude more potent than the parent antibiotic tobramycin, the membrane-targeting antimicrobial peptide mixture gramicidin D, and the cationic lipopeptide polymyxin B, which are in clinical use.
源自氨基糖苷类假寡糖抗生素的抗菌阳离子两亲物会干扰细菌膜的结构和功能，为新型抗生素的开发提供了一个有前景的方向。在此，我们报告了源自假三糖氨基糖苷妥布霉素及其假二糖片段奈替米星的阳离子两亲物的设计与合成。研究了抗菌活性、膜选择性、作用方式和构效关系。几种阳离子两亲物表现出显著的抗菌活性，一种两亲性奈替米星衍生物对所有测试的细菌菌株均有效；此外，针对几种测试菌株，该化合物的效力比临床使用的母体抗生素妥布霉素、靶向膜的抗菌肽混合物短杆菌肽D和阳离子脂肽多粘菌素B高出一个数量级以上。
