Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin

AIM:To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities.METHODS:Acetic,propionic,and butyric anhydride were reacted with mangiferin,respectively.The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin(STZ),and the islet cells were checked by biopsy inspection.RESULTS:7,2',3',4',6'-penta-acetyl-mangiferin(PAM),3,6,7,2',3',4',6'-hepta-propionyl-mangiferin(HPM) and 3,6,7,2',3',4'-hexa-butyryl-mangiferin(HBM) were synthesized and their structures were identified by MS,1H,13C NMR,and 2D NMR.These three compounds were reported for the first time.PAM group(0.5,0.25 mmol·kg-1),HPM group(0.5,0.25 mmol·kg-1),and HBM group(0.5,0.25,0.125 mmol·kg-1) mice showed strong hypoglycemic activity(P-1),PAM group(0.125 mmol·kg-1) and HPM group(0.125 mmol·kg-1) showed marginal hypoglycemic activity(P-1) had the potential for a hypoglycemic effect,although it did not demonstrate that statistically.In histological examination,the islet cells of the PAM,HPM,and HBM groups could recover from the STZ damage;islet cells of the mangiferin group could recover also,but less than the esterified-derivative groups.CONCLUSIONS:Derivatives could repair the damaged islet cells,and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself.There existed a structure activity effect,and a solubility effect relationship:the larger esterification moieties,or the higher lipid-solubility,the stronger the hypoglycemic activity(no ester→acetyl→propionyl→butyryl).Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.