Discovery of C-9 Modified Berberine Derivatives as Novel Lipid-Lowering Agents

Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as promising lipid-lowering agent in the field drug repurposing. Particularly, chemical modification at C-9 position BBR can remarkably improve its efficacy. In this study, thirteen novel derivatives were rationally designed, synthesized, and evaluated by preliminary tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared simvastatin. Among these compounds, compound 2h-1 2h-2 better activity profiling four tests involving inhibition total cholesterol (TCHO), triglyceride (TG), low-density lipoprotein (LDLC) increase high-density (HDLC). Correspondingly, analogs 9-O-cinnamic moiety probably activity, should be exploited an important versatile template for development BBR-like agents.