Tobramycin and nebramine as pseudo-oligosaccharide scaffolds for the development of antimicrobial cationic amphiphiles

Yifat Berkov-Zrihen, Ido M. Herzog, Raphael I. Benhamou, Mark Feldman, Kfir B. Steinbuch, Pazit Shaul, Shachar Lerer, Avigdor Eldar, Micha Fridman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4340-4349
Number of pages10
JournalChemistry - A European Journal
Volume21
Issue number11
DOIs
StatePublished - 9 Mar 2015

Keywords

  • antibiotic resistance
  • antibiotics
  • bacterial membranes
  • cationic amphiphiles
  • glycosides

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