[摘要]：A facile synthetic protocol for the prodn. of neomycin B derivs. with various modifications at the 5'' position has been developed. The structural activity relation (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AMEs) was investigated. Enzymic and mol. modeling studies reveal that the superb substrate promiscuity of AMEs allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivs. show enhanced antibacterial activity compared to the parent neomycin. Surprisingly, when testing synthetic neomycin derivs. against other human pathogens, two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert a high level of resistance against clin. used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that new biol. and antimicrobial activities can be obtained by chem. modifications of old drugs.
