title: Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin derivatives.
abstract: 5-Deoxy-5-episubstituted arbekacin derivatives have been designed and efficiently synthesized. The synthetic compounds showed potent antibacterial activity against both Staphylococcus aureus, including methicillin-resistant S. aureus, and Pseudomonas aeruginosa. In particular, these derivatives were superior to arbekacin against MRSA strains expressing the bifunctional aminoglycoside-modifying enzyme AAC(6')-APH(2''). The antibacterial activity of the 5-deoxy-5-episubstituted arbekacin derivatives against Pseudomonas aeruginosa was markedly influenced by the efflux system of MexXY/OprM. The 6'-N-methyl derivative of the 5-epi arbekacin was effective against Pseudomonas aeruginosa expressing the aminoglycoside-modifying enzyme AAC(6').
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hiraiwa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Usui
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Maebashi
authors.forename: Nobuto
authors.initials: N
authors.lastname: Minowa
authors.forename: Daishiro
authors.initials: D
authors.lastname: Ikeda
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D008712:Methicillin / Q000737:chemistry; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D003982:Dibekacin; C031986:arbekacin; D008712:Methicillin