Design, synthesis, and biological activity of 9-O-cinnamoylberberines as novel lipid-lowering agents

Berberine possesses a wide spectrum of lipid regulation, and yet it has poor physicochemical property and cytotoxicity as a drug candidate. In order to alleviate the problems, a total of twenty-one 9--cinnamoylberberines and twenty 9--cinnamoyltetrahydroberberines were designed, synthesized, and evaluated by cell viability experiment and four classical lipid-lowering assays involving with total cholesterol, triglyceride, low density lipoprotein cholesterol, and high density lipoprotein cholesterol. A structure-activity relationship study of these compounds resulted in the discovery of two promising candidate molecules ( and ). Compound displayed the most potent inhibitory effect for TG formation, with the inhibitory rates of 40.5% and 76.8% in 3T3-L1 cells and HepG2 cells, respectively. Compound exhibited the most promoting activity for the production of HDLC, with the increasing rates of 52.6% and 70.5% in both models, respectively. These two attractive compounds can be further investigated as new lipid-lowering agents in follow-up researches.