title: Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives.
abstract: 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.
authors.affiliation: Universite de Grenoble I/CNRS, UMR 5063, Departement de Pharmacochimie Moleculaire, ICMG FR 2607, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baussanne
authors.forename: Antoine
authors.initials: A
authors.lastname: Bussière
authors.forename: Somnath
authors.initials: S
authors.lastname: Halder
authors.forename: Carine
authors.initials: C
authors.lastname: Ganem-Elbaz
authors.forename: Myriam
authors.initials: M
authors.lastname: Ouberai
authors.forename: Mickael
authors.initials: M
authors.lastname: Riou
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Paris
authors.forename: Eric
authors.initials: E
authors.lastname: Ennifar
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Décout
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002151:Calorimetry; D005601:Framycetin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D005601:Framycetin; C488396:neamine