title: Tobramycin and nebramine as pseudo-oligosaccharide scaffolds for the development of antimicrobial cationic amphiphiles.
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.
authors: School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801 (Israel).
authors: Yifat
authors: Y
authors: Berkov-Zrihen
authors: Ido M
authors: IM
authors: Herzog
authors: Raphael I
authors: RI
authors: Benhamou
authors: Mark
authors: M
authors: Feldman
authors: Kfir B
authors: KB
authors: Steinbuch
authors: Pazit
authors: P
authors: Shaul
authors: Shachar
authors: S
authors: Lerer
authors: Avigdor
authors: A
authors: Eldar
authors: Micha
authors: M
authors: Fridman
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D015394:Molecular Structure; D009844:Oligosaccharides; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry*; D014031:Tobramycin / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D009844:Oligosaccharides; D013501:Surface-Active Agents; D014031:Tobramycin
keywords: antibiotic resistance; antibiotics; bacterial membranes; cationic amphiphiles; glycosides