A novel structural class of coumarin-chalcone fibrates as PPAR alpha/gamma agonists with potent antioxidant activities: Design, synthesis, biological evaluation and molecular docking studies

作者：Niu, Handong; Wang, Wenbao; Li, Jinyan; Lei, Yu; Zhao, Yong; Yang, Weixu; Zhao, Chaoyue; Lin, Bin; Song, Shaojiang^*; Wang, Shaojie^*

来源：European Journal of Medicinal Chemistry, 2017, 138: 212-220.

DOI：10.1016/j.ejmech.2017.06.033

• Fibrates
• Coumarin-chalcone
• PPAR alpha/gamma agonists
• Antioxidant activity

A series of structurally interesting coumarin-chalcone fibrates were synthesized and evaluated for their PPAR alpha/gamma agonist activities and antioxidant activities. Among these compounds, compounds 5a, 5d, and 7a were identified as potent PPAR alpha and gamma dual agonists, and their PPAR alpha agonist activities were found to be more potent than that of Fenofibrate. Furthermore, the results of antioxidant investigations revealed that compounds 5d and 6a-6d had greater potency than Trolox with IC50 values ranging from 9.40 mu M to 18.63 mu M. The structure-activity relationship revealed that the electron-withdrawing nitro group substituted at the C6' position of the benzopyran moiety increased the PPAR alpha and gamma agonist efficacy. Moreover, the presence of a double bond on the benzopyran moiety was essential for PPAR alpha and gamma agonist efficacy. The agonist activity of PPAR alpha exhibited by compound 5d was examined by molecular docking studies. Taken together, the results we obtained showed that compound 5d had the potential to be a lead compound for further research.

• 出版日期2017-9-29
• 单位沈阳药科大学