Format

Send to

Choose Destination
See comment in PubMed Commons below
ChemMedChem. 2014 Sep;9(9):2164-71. doi: 10.1002/cmdc.201402175. Epub 2014 Jul 23.

Singly modified amikacin and tobramycin derivatives show increased rRNA A-site binding and higher potency against resistant bacteria.

Author information

  • 1Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).

Abstract

Semisynthetic derivatives of the clinically useful aminoglycosides tobramycin and amikacin were prepared by selectively modifying their 6'' positions with a variety of hydrogen bond donors and acceptors. Their binding to the rRNA A-site was probed using an in vitro FRET-based assay, and their antibacterial activities against several resistant strains (e.g., Pseudomonas aeruginosa, Klebsiella pneumonia, MRSA) were quantified by determining minimum inhibitory concentrations (MICs). The most potent derivatives were evaluated for their eukaryotic cytotoxicity. Most analogues displayed higher affinity for the bacterial A-site than the parent compounds. Although most tobramycin analogues exhibited no improvement in antibacterial activity, several amikacin analogues showed potent and broad-spectrum antibacterial activity against resistant bacteria. Derivatives tested for eukaryotic cytotoxicity exhibited minimal toxicity, similar to the parent compounds.

KEYWORDS:

A-site rRNA; aminoglycosides; antibiotics; drug-resistant bacteria

PMID:
25055981
PMCID:
PMC4298452
DOI:
10.1002/cmdc.201402175
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center