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.
Bera
Smritilekha
S
Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
Zhanel
George G
GG
Schweizer
Frank
F
D000480:Alkynes / Q000737:chemistry; D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D005601:Framycetin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D007612:Kanamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D000480:Alkynes; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010455:Peptides; D014230:Triazoles; D005601:Framycetin; D007612:Kanamycin; D003300:Copper