Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance

Pazit Shaul, Keith D. Green, Roi Rutenberg, Maria Kramer, Yifat Berkov-Zrihen, Elinor Breiner-Goldstein, Sylvie Garneau-Tsodikova, Micha Fridman

Research output: Contribution to journalArticlepeer-review


Amongst the many synthetic aminoglycoside analogues that were developed to regain the efficacy of this class of antibiotics against resistant bacterial strains, the 1-N-acylated analogues are the most clinically used. In this study we demonstrate that 6′-N-acylation of the clinically used compound tobramycin and 6′′′-N-acylation of paromomycin result in derivatives resistant to deactivation by 6′-aminoglycoside acetyltransferase (AAC(6′)) which is widely found in aminoglycoside resistant bacteria. When tested against AAC(6′)- or AAC(3)-expressing bacteria as well as pathogenic bacterial strains, some of the analogues demonstrated improved antibacterial activity compared to their parent antibiotics. Improvement of the biological performance of the N-acylated analogues was found to be highly dependent on the specific aminoglycoside and acyl group. Our study indicates that as for 1-N-acylation, 6′- and 6′′′-N-acylation of aminoglycosides offer an additional promising direction in the search for aminoglycosides capable of overcoming infections by resistant bacteria.

Original languageEnglish
Pages (from-to)4057-4063
Number of pages7
JournalOrganic and Biomolecular Chemistry
Issue number11
StatePublished - 7 Jun 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry


Dive into the research topics of 'Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance'. Together they form a unique fingerprint.

Cite this