Synthesis and hypoglycemic activity evaluation of rhein amide derivatives

In order to investigate the relationship of the structure and hypoglycemic activity, rhein amide derivatives 2a–2e were synthesized and their hypoglycemic activities were evaluated by glucose consumption in HepG2. Their structures were characterized by 1H-, 13C NMR, IR, mass and elemental analysis. All the compounds exhibited strong hypoglycemic activity in improving glucose consumption in HepG2 cell assays in vitro, which was influenced by the diversity of rhein amide derivatives. The compounds 2a–c, 2f, and 2g bearing heterocyclic ring were proved to be more potentially useful in glucose consumption than dimethyldiguanide. Among all the compounds, compound 2f exhibited the strongest activity on glucose consumption, while compound 2d showed the weakest activity.