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

Abstract

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.

Graphical Abstract

Keywords:

• Antidiabetic
• cycloaddition
• indolizine
• hypoglycemic activity
• prodrugs

Acknowledgments

The researchers are indebted to Acharya & BM Reddy College of Pharmacy, Bengaluru, India, for providing the essential research facilities. Indian Institute of Science also has to be thanked for providing spectral data.

Disclosure statement

The authors declare that they have no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.