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
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.