TY - JOUR
T1 - Tobramycin and nebramine as pseudo-oligosaccharide scaffolds for the development of antimicrobial cationic amphiphiles
AU - Berkov-Zrihen, Yifat
AU - Herzog, Ido M.
AU - Benhamou, Raphael I.
AU - Feldman, Mark
AU - Steinbuch, Kfir B.
AU - Shaul, Pazit
AU - Lerer, Shachar
AU - Eldar, Avigdor
AU - Fridman, Micha
N1 - Publisher Copyright:
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA.
PY - 2015/3/9
Y1 - 2015/3/9
N2 - 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.
AB - 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.
KW - antibiotic resistance
KW - antibiotics
KW - bacterial membranes
KW - cationic amphiphiles
KW - glycosides
UR - http://www.scopus.com/inward/record.url?scp=84923646618&partnerID=8YFLogxK
U2 - 10.1002/chem.201406404
DO - 10.1002/chem.201406404
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C2 - 25156402
AN - SCOPUS:84923646618
SN - 0947-6539
VL - 21
SP - 4340
EP - 4349
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 11
ER -