Study On Synthesis And Anti-diabetes Activity Of Tiliroside Derivantives

Objective Tiliroside was the main constituent for the anti-diabetes activity in Chinese herb potentilla.Tiliroside showed low effect and toxic effect in the previous work.However,the pharmacokinetics research for tiliroside showed that the compound was decomposed quickly by carboxylesterase in vivo.The potential pharmcophores of tiliroside were retained and then connected by ether bond.The derivatives were synthesized by organic chemistry methods and the activities for anti-diabetes of the derivatives were evaluated,and then the lead compounds could be obtained.Finally,the preliminary structure activity relationship could be gained.Methods 1.The synthesis of derivatives:the derivatives were synthesized by Claisen-Schimidt reaction,a-bromination of the ?,?-unsaturated ketone and the etherification reaction.All the compounds were identified by organic spectrum methods.2.Evaluation of the anti-diabetes activity of the derivatives:all the derivatives were investgated for the glucose consumption of the insulin resistance HepG2 cells by the glucose oxidase methods.3.The study on structure activity relationship:the possible mechanism of all the derivatives was applied with the moleculer docking.Results 1.There were forty six compounds synthesized by organic chemistry methods,including twenty two intermediates and twenty four derivatives.All the compounds were i identified by organic spectrum methods.All the derivatives were the new compounds which didn' t report before.2.Most of the derivatives could improve the glucose consumption of the insulin resistance HepG2 cell,beside compound A3,A4,A9,A10,B7,C2 could could improve the glucose consumption Significant.3.The docking results showed that the compounds acted on glucokinas with the hydrogen bond and hydrophobic bond.The compound A3,B7 and C2 got high score.This results could be correspondence with the glucose consumption experiments.Conclusion The new derivatives were designed on the basis of the previous synthesized work and the pharmacokinetics research.The twenty four derivatives were prepared from the substituted benzaldehyde through Claisen-Schimidt reaction,? bromination of the a,?-unsaturated keto and the etherification reaction.iliroside derivatives showed the good activities in glucose consumption experiments.the ability of most derivatives for improving the glucose consumption is better than kaempferol and tiliroside.The structure activity relationship showed that the cinnamoyl fragment and kaempferol were the necessary pharmcophores,men while the number of cinnamoyl didn't affected the activities.The activities could be better when the aromatic hydrogen atom was substitute by hydrophobic group.However,the activities could be worse when the aromatic hydrogen atom was substitute by hydrophilic group.the moleculer docking experiments showed that the derivatives improved the glucose consumption in insulin-resistance HepG2 cells by activated the glucokinase.