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.

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