Synthesis of 2''-amino-2''-deoxyarbekacin and its analogs having potent activity against methicillin-resistant Staphylococcus aureus.
Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2''-Amino-2''-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.
Kondo
S
S
Institute of Microbial Chemistry, Tokyo, Japan.
Ikeda
Y
Y
Ikeda
D
D
Takeuchi
T
T
Usui
T
T
Ishii
M
M
Kudo
T
T
Gomi
S
S
Shibahara
S
S
D002240:Carbohydrate Sequence; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013210:Staphylococcus / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
C089087:2''-amino-2''-deoxyarbekacin; D003982:Dibekacin