Toward overcoming staphylococcus aureus aminoglycoside resistance mechanisms with a functionally designed neomycin analogue

Stephen Hanessian, Alexandre Giguère, Justyna Grzyb, Juan Pablo Maianti, Oscar M. Saavedra, James B. Aggen, Martin S. Linsell, Adam A. Goldblum, Darin J. Hildebrandt, Timothy R. Kane, Paola Dozzo, Micah J. Gliedt, Rowena D. Matias, Lee Ann Feeney, Eliana S. Armstrong

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Deoxygenation of the diol groups in rings A and D of neomycin in combination with the introduction of an N1-(l)-HABA group in the 2-deoxystreptamine subunit (ring B) leads to a novel and potent antibiotic (1) with activity against strains of S. aureus carrying known aminoglycoside resistance determinants, as well as against an extended panel of Methicillin-resistant S. aureus isolates (n = 50). Antibiotic 1 displayed >64 fold improvement in MIC 50 and MIC 90 against this MRSA collection when compared to the clinically relevant aminoglycosides amikacin and gentamicin. The synthesis was achieved in six steps and 15% overall yield.

Original languageEnglish (US)
Pages (from-to)924-928
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume2
Issue number12
DOIs
StatePublished - Dec 8 2011
Externally publishedYes

Keywords

  • Aminoglycoside
  • antibiotics
  • deoxygenation
  • enzymatic modification
  • MRSA
  • neomycin analogues
  • resistance

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Toward overcoming staphylococcus aureus aminoglycoside resistance mechanisms with a functionally designed neomycin analogue'. Together they form a unique fingerprint.

Cite this