Studies On Synthesis And Structure-activity Relationships On Cinnamoyl Derivatives Of Trans-tiliroside

Potentilla chinensis Bge (Rosaceae) is widely distributed in most place of China. As a folk medicine, it has been used to reduce swelling and staunch bleeding, and has anti-inflammatory and detoxification properties. In addition, P. chinensis revealed the therapeutic effect for controlling blood glucose and improving glucose tolerance of body in clinic. Our previous study showed that the extract from P. chinensis revealed significant anti-diabetic activities, and one main anti-daibetic constituent, Kaempferol-3-O-β-D-(6-O-trans-p-coumaroyl)glucopyranside was isolated and identified from this extract of P. chinensis.The structure of Kaempferol-3-O-β-D-(6-O-trans-p-coumaroyl)glucopyranside is different from biguanides, sulfonylureas, a-glucosidase inhibitors, thiazolidined iones and GLP-1receptor agonists on the market, which indicates above lead compound may be has different anti-diabetic mechanism.This paper deals with the synthesis and structure-activity relationships on cinnamoyl derivatives of trans-tiliroside. Derivative synthesis was schemed from Kaempferol through Koenigs-Knorr reaction with glycosyl bromides, deacetylation, esterification, hydrogenation and Knoevenagel-Doebner reaction to yield derivative compounds. As a result,8target compounds, including six new compounds (4,5-9) have been synthesized and their structures were elucidated by analyses of NMR and MS spectra. The anti-diabetic screening was undertaken by using alloxan mice model. Comparing with the model control group, Compound2,3,5,7,8, cinnamic acid and tiliroside could decrease the blood glucose level of alloxan mice. Compound7showed significant anti-diabetic activity, and it is worth to take further research.To identify antidiabetic targets for tiliroside using reverse docking method, we found that the tiliroside has good binding affinity with aldose reductase, β-grucosidase and dipeptidyl peptidase Ⅳ.