title: Synthesis, in vitro antimycobacterial and antibacterial evaluation of IMB-070593 derivatives containing a substituted benzyloxime moiety.
abstract: A series of novel IMB-070593 derivatives containing a substituted benzyloxime moiety and displaying a remarkable improvement in lipophilicity were synthesized and evaluated for their in vitro antimycobacterial and antibacterial activity. Our results reveal that the target compounds 19a-m have considerable Gram-positive activity (MIC: <0.008-32 µg/mL), although they are generally less active than the reference drugs against the Gram-negative strains. In particular, compounds 19h, 19j, 19k and 19m show good activity (MICs: <0.008-4 µg/mL) against all of the tested Gram-positive strains, including ciprofloxacin (CPFX)- and/or levofloxacin (LVFX)-resistant MSSA, MRSA and MSSE. Moreover, compound 19l (MIC: 0.125 µg/mL) is found to be 2-4 fold more active than the parent IMB070593, CPFX and LVFX against M. tuberculosis H37Rv ATCC 27294.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Zengquan
authors.initials: Z
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Mingliang
authors.initials: M
authors.lastname: Liu
authors.forename: Sujie
authors.initials: S
authors.lastname: Li
authors.forename: Lanying
authors.initials: L
authors.lastname: Sun
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Guo
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D064704:Levofloxacin; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D015242:Ofloxacin / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; C583739:IMB-070593; D010091:Oximes; D010880:Piperidines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin
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