Evaluation of amphiphilic aminoglycoside-peptide triazole conjugates as antibacterial agents

The solid-and solution-phase synthesis of amphiphilic aminoglycoside-peptide triazole conjugates (APTCs) accessed by copper(I)-catalyzed 1,3-dipolar cycloaddition reaction between a hydrophobic and ultrashort peptide-based alkyne and a neomycin B-or kanamycin A-derived azide is presented. Antibacterial evaluation demonstrates that the antibacterial potency is affected by the nature of the peptide component. Several APTCs exhibit superior activity against neomycin B-and kanamycin A-resistant strains when compared to their parent aminoglycoside while displaying reduced activity against neomycin B-and kanamycin A-susceptible strains. (C) 2010 Elsevier Ltd. All rights reserved.