Synthesis and Biological Activity of Mono- and Di-N-acylated Aminoglycosides

Nishad Thamban Chandrika, Keith D. Green, Jacob L. Houghton, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Despite issues with oto/nephrotoxicity and bacterial resistance, aminoglycosides (AGs) remain an effective and widely used class of antibacterial agents. For decades now, efforts toward the development of novel AGs with potential to overcome some of these problems have been major research focuses. 1-N-Acylation, especially γ-amino-β-hydroxybutyrate (AHB) derivatization, has proven to be one of the most successful strategies for improving the overall properties of AGs, including their ability to avoid certain resistance mechanisms. More recently, 6′-N-acylation arose as another possible strategy to improve the properties of these drugs. In this study, we report on the glycinyl, carboxybenzyl, and AHB mono- and diderivatization at the 1-, 6′-, and/or 4⌄-amines of the AGs amikacin, kanamycin A, netilmicin, sisomicin, and tobramycin. We also present the antibacterial activities and the reduced reactivity of AG-modifying enzymes (AMEs) toward these new AG derivatives, and identify the AMEs present in the bacterial strains tested.

Original languageEnglish
Pages (from-to)1134-1139
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number11
StatePublished - Sep 30 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.


  • Acylation
  • aminoglycoside antibiotics
  • bacterial resistance
  • drug development
  • drug-modifying enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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