Tobramycin and Nebramine as Pseudo‐oligosaccharide Scaffolds for the Development of Antimicrobial Cationic Amphiphiles |
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| Authors: | Yifat Berkov‐Zrihen Ido M Herzog Raphael I Benhamou Dr Mark Feldman Kfir B Steinbuch Pazit Shaul Dr Shachar Lerer Dr Avigdor Eldar Dr Micha Fridman |
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| Affiliation: | 1. School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801 (Israel);2. Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801 (Israel) |
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| Abstract: | 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. |
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| Keywords: | cationic amphiphiles antibiotic resistance antibiotics bacterial membranes glycosides |
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