Synthesis Of Garbanzoin A, Formononetin, Genistein Derivatives In Chickpeas And Screening Of Insulin Resistance To HepG2 Cells

Objective of the research:Chickpeas?Cicer aretinum L.?,also known as pepper beans,chicken heart beans,chicken beans,etc,are the plant of Leguminosae Chickpeas and commonly used in Uighur medicine.Chickpeas can lower blood glucose,reduce blood lipid,protect the cardiovascular,promote bone formation and also have many other pharmacological effects,such as,anti-oxidation,anti-tumor,etc.The research results showed that the isoflavones of Chickpeas can lower blood glucose.Chickpeas contain the chemical constituents of isoflavones of Biochanin A,Formononetin,Genistein.However,the activity of lowering blood glucose of these isoflavones monomer compounds is not obvious.In order to improve the activity of lowering blood glucose of the monomer compounds,the structure of the isoflavones had been modified according to the organic chemistry knowledge,and the activity of lowering blood glucose of the modified derivatives had been studied.Thus laying the the foundation of material structure for future research and development of new drugs for the treatment of diabetes.Research method:In this paper,a lot of domestic and foreign literature were reviewed,and the structural modification and pharmacological effects of Biochanin A,Formononetin and Genistein were reviewed,and 79 references were cited.The structural modification studies were carried out on the Biochanin A,Formononetin and Genistein,and the results showed that the modification at phenolic hydroxyl groups of isoflavones could improve their pharmacological activity.In order to improve the isoflavones solubility and improve the targeting of isoflavones,the experiment was carried out by isobutyrylation reaction,benzenesulfonylation reaction,4-bromobutyryl reaction,isobutylation reaction,n-butyrylation reaction,phosphorylation reaction,and the EDC condensation reaction with phenylpropionic acid,p-trifluoromethyl phenylacetic acid,and the etherification reaction with 1,3-dibromopropane,1-bromopropane,3-bromopropene,and the Mannich reaction bteween Formononetin and n-butylamine.The modified derivatives were separated and purified bysilica gel column chromatography.The structures were identifued by ¹H-NMR,¹³C-NMR and high-resolution mass spectrometry.HepG2 cell model was established,and the modified derivatives were screened for lowering blood glucose activity.The modified derivatives with better lowering blood glucose activity were screened out by statistical analysis.Research results:A total of 36 modified derivatives were separated and identified by structural modification of Biochanin A,Formononetin and Genistein.Eight compounds are new compounds,which ensures structural diversity and novelty for lowering blood glucose activity screening.The lowering blood glucose activity was screened by insulin resistance HepG2 cell model.and the Biochanin A-7-benzenesulfonate,Formononetin-7-p-trifluoromethyl phenylacetate,Genistein-7-propyl ether have a good lowering blood glucose activity.Conclusion:The structure of Biochanin A,Formononetin and Genistein were modified,and the derivatives with structural novelty are obtained,the lowering blood glucose activity was screened by using the insulin resistance HepG2 cell model,obtained the modified derivatives with better lowering blood glucose activity than the parent itself,but their activities are not as positive as metformin.