Abstract
Coumarin moiety has garnered momentous attention especially in the design of compounds with significant biological activities. In this work, a series of 3-substituted coumarin derivatives 6a-6l were synthesized and fully characterized. Most of the compounds could obviously inhibit the activity of cyclooxygenase-1 (COX-1) at the concentration of 10 µM. Besides, 6h and 6l exhibited highest inhibitory effects against COX-2 with inhibition rates of 33.48 and 35.71%, respectively. Detailed structure-activity relationships (SARs) were also discussed. In vivo studies, 6b, 6i and 6l could remarkably repress the xylene-induced ear swelling in mice at the dose of 20 mg/kg. Especially, 6l seemed to be the most effective compound at the dose of 10 mg/kg, displaying favorable anti-inflammatory activity comparable to indomethacin. All of these findings suggested that 6l might be utilized as a candidate for the treatment of inflammatory diseases.
Keywords:
3-substituted coumarin; anti-inflammatory; cyclooxygenase; tumor necrosis factor; xylene-induced ear swelling.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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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 Survival / drug effects
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Coumarins / chemical synthesis
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Coumarins / chemistry
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Coumarins / pharmacology*
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Drug Design*
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Ear Diseases / chemically induced
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Ear Diseases / drug therapy*
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Mice
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Molecular Structure
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RAW 264.7 Cells
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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 / biosynthesis
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Xylenes
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Coumarins
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Cyclooxygenase Inhibitors
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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Xylenes
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coumarin
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Cyclooxygenase 1
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Cyclooxygenase 2