Synthesis and biological evaluation of tetrahydrocoptisine quaternary ammonium compounds.
- Author:
Dong-Mei WANG
1
;
Jin-Zhao WEI
;
Bao-Yan FAN
;
Quan LIU
;
Hai-Bo ZHU
;
Zhu-Fang SHEN
;
Song WU
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Berberine Alkaloids;
chemical synthesis;
chemistry;
pharmacology;
Cholesterol;
blood;
Glucose;
metabolism;
Hep G2 Cells;
Humans;
Hyperlipidemias;
blood;
Hypoglycemic Agents;
chemical synthesis;
chemistry;
pharmacology;
Hypolipidemic Agents;
chemical synthesis;
chemistry;
pharmacology;
Mesocricetus;
Mice;
Molecular Structure;
Quaternary Ammonium Compounds;
chemical synthesis;
chemistry;
pharmacology;
Structure-Activity Relationship;
Triglycerides;
blood
- From:
Acta Pharmaceutica Sinica
2012;47(12):1640-1645
- CountryChina
- Language:Chinese
-
Abstract:
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.
