Abstract
A series of novel oxazolidinone compounds with a substituted ligustrazine C-ring unit and different substituted groups at the C-5 side chain were designed and synthesized using linezolid as a lead and based on a scaffold hopping strategy. Their antibacterial and anti-inflammatory activities were evaluated. The results of in vitro antibacterial assays showed that all fourteen target compounds displayed potent activity against Gram-positive pathogens, particularly 8b, 13b, 14a, 14b, 15a, and 15b. Moreover, 14a and 14b exhibited significant inhibitory activities on the production of inflammatory mediators, including nitric oxide, interleukin-6, and tumor necrosis factor-alpha. Thus, these derivatives could serve as valuable candidates to develop anti-infective agents for the treatment of chronic wounds.
Keywords:
anti-inflammatory; antibacterial; ligustrazine; linezolid; oxazolidinone.
© 2015 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cell Line / drug effects
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Cell Line / metabolism
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Chemistry Techniques, Synthetic
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Drug Evaluation, Preclinical / methods
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Gram-Positive Bacteria / drug effects
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Mice
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Microbial Sensitivity Tests
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Nitric Oxide / metabolism
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Oxazolidinones / chemistry*
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Pyrazines / chemistry
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Bacterial Agents
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-6
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Lipopolysaccharides
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Oxazolidinones
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Pyrazines
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Tumor Necrosis Factor-alpha
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interleukin-6, mouse
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Nitric Oxide
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tetramethylpyrazine