Synthesis and biological evaluation of tetrahydrocoptisine quaternary ammonium compounds

The goal of treatment of metabolic syndrome is the prevention of diabetes and cardiovascular events.  A series of novel tetrahydrocoptisine quaternary ammonium compounds were prepared to evaluate their action of hypoglycemia and hypolipidemia for finding the therapeutic agents of metabolic syndrome.  Starting from the coptisine hydrochloride (2), fifteen target compounds were synthesized by reduction and substitution of the 7-N position.  All of the target compounds were characterized by ¹H NMR and HR-MS.  Their hypoglycemic activities were evaluated in HepG2 cell and hypolipidemic activities of compounds with better hypoglycemic activity were tested further in vivo.  Results indicated that compounds 5, 7, 8 and 9 exhibited better hypoglycemic activities in vitro and compounds 5 and 8 exhibited good hypolipidemic activities in high-fat-diet (HFD) induced hyperlipidemia mice and (or) hamsters.  However, the activity is not as good as simvastatin.