title: Synthesis and antibacterial activity of 4″ or 6″-alkanoylamino derivatives of arbekacin.
abstract: Arbekacin, an aminoglycoside antibiotic, is an important drug because it shows a potent efficacy against methicillin-resistant Staphylococcus aureus. However, resistance to arbekacin, which is caused mainly by the bifunctional aminoglycoside-modifying enzyme, has been observed, becoming a serious problem in medical practice. To create new arbekacin derivatives active against resistant bacteria, we modified the C-4″ and 6″ positions of its 3-aminosugar portion. Regioselective amination of the 6″-position gave 6″-amino-6″-deoxyarbekacin (1), and it was converted to a variety of 6″-N-alkanoyl derivatives (6a-z). Furthermore, regioselective modifications of the 4″-hydroxyl group were performed to give 4″-deoxy-4″-epiaminoarbekacin (2) and its 4″-N-alkanoyl derivatives (12 and 13). Their antibacterial activity against S. aureus, including arbekacin-resistant bacteria, was evaluated. It was observed that 6″-amino-6″-N-[(S)-4-amino-2-hydroxybutyryl]-6″-deoxyarbekacin (6o) showed excellent antibacterial activity, even better than arbekacin.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurihara
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Hiyoshi, Kawasaki, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Akamatsu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D003982:Dibekacin; C031986:arbekacin