1. J Med Chem. 2016 Oct 27;59(20):9350-9369. Epub 2016 Oct 17.

New Broad-Spectrum Antibacterial Amphiphilic Aminoglycosides Active against
Resistant Bacteria: From Neamine Derivatives to Smaller Neosamine Analogues.

Zimmermann L(1), Das I(1), Désiré J(1), Sautrey G(2), Barros R S V(1), El Khoury 
M(2), Mingeot-Leclercq MP(2), Décout JL(1).

Author information: 
(1)Département de Pharmacochimie Moléculaire, ICMG FR 2607, University Grenoble
Alpes/CNRS, UMR 5063 , 470 Rue de la Chimie, BP 53, F-38041 Grenoble, France.
(2)Unité de Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research
Institute, Université Catholique de Louvain , Avenue E. Mounier 73, B1.73.05,
B-1200 Brussels, Belgium.

Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum
antibiotics disturbing protein synthesis through binding to the A site of 16S
rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical
efficacy through the selection of resistant bacteria. Recently, conjugation of
lipophilic groups to AGs generated a novel class of potent antibacterial
amphiphilic aminoglycosides (AAGs) with significant improved activities against
various sensitive and resistant bacterial strains. We have identified amphiphilic
3',6-dialkyl derivatives of the small aminoglycoside neamine as broad spectrum
antibacterial agents targeting bacterial membranes. Here, we report on the
synthesis and the activity against sensitive and resistant Gram-negative and/or
Gram-positive bacteria of new amphiphilic 3',4'-dialkyl neamine derivatives and
of their smaller analogues in the 6-aminoglucosamine (neosamine) series prepared 
from N-acetylglucosamine.

DOI: 10.1021/acs.jmedchem.6b00818 
PMID: 27690420  [PubMed - in process]