Design, synthesis and chemical stability of indolizine derivatives for antidiabetic activity

Prodrugs of metformin were synthesized with the goal of enhancing biological activity of metformin. They were synthesized by combining metformin with 2-substituted indolizine (C7-C12). The synthesized prodrugs were characterized by IR, 1H NMR, 13C NMR, and mass spectroscopy. The chemical hydrolysis of C7-C12 was carried out at pH 1.2, 6.8, and 7.4. All compounds showed encouraging chemical stability at pH 1.2 and 6.8, whereas mild hydrolysis was shown at pH 7.4. Further prodrugs were screened for antidiabetic activity using a streptozotocin-induced model in rat. These derivatives showed substantial results. Among them C8 showed significant activity in the reduction of streptozotocin-induced blood glucose in rats when compared to that of metformin, indicating the effectiveness of prodrug.