1. J Med Chem. 2010 Jan 14;53(1):119-27.

Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives.

Baussanne I, Bussière A, Halder S, Ganem-Elbaz C, Ouberai M, Riou M, Paris JM,
Ennifar E, Mingeot-Leclercq MP, Décout JL.

Universite de Grenoble I/CNRS, UMR 5063, Departement de Pharmacochimie
Moleculaire, ICMG FR 2607, France.

The aminoglycoside antibiotics bind to the 16S bacterial rRNA and disturb the
protein synthesis. One to four hydroxyl functions of the small aminoglycoside
neamine were capped with phenyl, naphthyl, pyridyl, or quinolyl rings. The 3',4'-
(6), 3',6- (7a), and the 3',4',6- (10a) 2-naphthylmethylene derivatives appeared 
to be active against sensitive and resistant Staphylococcus aureus strains. 10a
also showed marked antibacterial activities against Gram (-) bacteria, including 
strains expressing enzymes modifying aminoglycosides, efflux pumps, or rRNA
methylases. 7a and 10a revealed a weak and aspecific binding to a model bacterial
16S rRNA. Moreover, as compared to neomycin B, 10a showed a lower ability to
decrease (3)H leucine incorporation into proteins in Pseudomonas aeruginosa. All 
together, our results suggest that the 3',4',6-tri-2-naphthylmethylene neamine
derivative 10a should act against Gram (-) bacteria through a mechanism different
from inhibition of protein synthesis, probably by membrane destabilization.

PMID: 20000576 [PubMed - indexed for MEDLINE]