Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin

• Published in: Chinese journal of natural medicines Vol. 11; no. 3; pp. 296 - 301
• Main Authors: LI, Xue-Jian, DU, Zheng-Cai, HUANG, Yan, LIU, Bu-Ming, HU, Wen-Ji, LU, Wen-Jie, DENG, Jia-Gang
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.05.2013
• Subjects: animal models; Animals; biopsy; Diabetes Mellitus, Experimental - drug therapy; drugs; Esterification; glycemic effect; Humans; Hypoglycemic activity; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; islets of Langerhans; Islets of Langerhans - drug effects; Male; Mangiferin derivatives; Mice; Molecular Structure; nuclear magnetic resonance spectroscopy; solubility; streptozotocin; Synthesis; Xanthones - administration & dosage; Xanthones - chemical synthesis; Xanthones - chemistry; Hypoglycemic activity; Mangiferin derivatives; Synthesis
• ISSN: 1875-5364; 1875-5364
• DOI: 10.1016/S1875-5364(13)60032-1

To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. 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. 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 < 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. 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.