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, 1 H, 13 C 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 < 0.01); mangiferin group (1, 0.5 mmol·kg −1 ), PAM group (0.125 mmol·kg −1 ) and HPM group (0.125 mmol·kg −1 ) showed marginal hypoglycemic activity ( P < 0.05); mangiferin group (0.25 mmol·kg −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. Conclusion 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.