Effect of varying the 4''-position of arbekacin derivatives on antibacterial activity against MRSA and Pseudomonas aeruginosa.
4''-Deoxy-4''-episubstituted arbekacin derivatives and 4''-epi-5-deoxy-5-episubstituted arbekacin derivatives were designed and synthesized. Arbekacin and 4''-epiarbekacin both displayed the same antibacterial activity against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)) and Pseudomonas aeruginosa. The 4''-epi-5-deoxy-5-episubstituted arbekacin derivatives showed potent antibacterial activity. Among them, the antibacterial activity of 5,4''-diepiarbekacin was superior to that of arbekacin or 5-episubstituted arbekacin against Gram-positive and Gram-negative bacteria. The 6'-N-methyl derivative of the 5,4''-diepiarbekacin was effective against P. aeruginosa expressing an aminoglycoside-modifying enzyme AAC(6')-Ib.
Hiraiwa
Yukiko
Y
Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Japan.
Minowa
Nobuto
N
Usui
Takayuki
T
Akiyama
Yoshihisa
Y
Maebashi
Kazunori
K
Ikeda
Daishiro
D
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D003982:Dibekacin; C031986:arbekacin