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Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin derivatives
Yukiko Hiraiwa1, Takayuki Usui, Yoshihisa Akiyama
1Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
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').
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