Synthesis and biological activity of novel tiliroside derivants

• Published in: European journal of medicinal chemistry 2011-10, Vol.46 (10), p.5189-5195
• Main Authors: Qin, Nan, Li, Chun-Bao, Jin, Mei-Na, Shi, Li-Huan, Duan, Hong-Quan, Niu, Wen-Yan
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase (ACC); Acetyl-CoA Carboxylase - metabolism; Adenosine 5′-monophosphate-activated protein kinase (AMPK); AMP-Activated Protein Kinases - metabolism; Anti-diabetic; Biological and medical sciences; Diabetes Mellitus, Type 2 - drug therapy; Enzyme Activation - drug effects; Flavonoids - chemical synthesis; Flavonoids - chemistry; Flavonoids - pharmacology; General and cellular metabolism. Vitamins; Glucose - metabolism; Hep G2 Cells; Humans; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Medical sciences; Pharmacology. Drug treatments; Plant Extracts - chemical synthesis; Plant Extracts - chemistry; Plant Extracts - pharmacology; Potentilla - chemistry; Tiliroside derivatives
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.07.059

A series of new tiliroside derivatives were synthesized and characterized by analytical 1H NMR, 13C NMR and mass spectrometry. All of the compounds were evaluated for anti-diabetic properties in vitro using HepG2 cells. Compounds 3c, 3d, and 3i– l caused significant enhancements in glucose consumption by insulin-resistant HepG2 cells compared with control cells and cells that were exposed to metformin (an anti-diabetic drug). Moreover, compound 3l significantly activated adenosine 5′-monophosphate-activated protein kinase activity and reduced acetyl-CoA carboxylase activity. Thus, the tiliroside derivative 3l offers potential to be developed as a new approach for treating type II diabetes. A new class of anti-diabetic agents, tiliroside derivatives were synthesized, and significantly activated AMPK, reduced ACC and enhanced glucose consumption in insulin resistance HepG2 cells in comparison with metformin. [Display omitted] ► Novel anti-diabetic tiliroside derivatives were synthesized. ► Six tiliroside derivatives showed stronger anti-diabetic activity than metformin. ► Compound 3l significantly activated AMPK, reduced ACC activity in a dose-dependent fashion.