Design, Synthesis and Evaluation of 3-Substituted Coumarin Derivatives as Anti-inflammatory Agents

Tao Wang; Tao Peng; Xiaoxue Wen; Gang Wang; Shuchen Liu; Yunbo Sun; Shouguo Zhang; Lin Wang

doi:10.1248/cpb.c19-01085

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Design, Synthesis and Evaluation of 3-Substituted Coumarin Derivatives as Anti-inflammatory Agents

Tao Wang, Tao Peng, Xiaoxue Wen, Gang Wang, Shuchen Liu, Yunbo Sun, Shouguo Zhang, Lin Wang

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Keywords: 3-substituted coumarin, anti-inflammatory, tumor necrosis factor, cyclooxygenase, xylene-induced ear swelling

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Supplementary material

2020 Volume 68 Issue 5 Pages 443-446

DOI https://doi.org/10.1248/cpb.c19-01085

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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.

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