Synthesis of Pyrazolo[۱,۲-b]phthalazine-۵,۱۰-dione Derivatives: A New Class of α –Glucosidase Inhibitors

Background: Hyperglycemia is a metabolic disorder that refers to an increase in blood sugar in diabetic patients. α-Glucosidase has been introduced as a membrane-bound enzyme, and it is the main enzyme for carbohydrate digestion in some parts of the intestine. Inhibition of α -glucosidase enzyme activity is a reliable approach to control post-prandial hyperglycemia condition. Objectives: In this study, a series of Pyrazolo[۱,۲-b]phthalazine-۵,۱۰-dione derivatives ۵a–t were synthesized via a multicomponent reaction and evaluated as new inhibitors for α-glucosidase. Methods: The biological activity of the synthesized compounds was studied using a source of the α-glucosidase enzyme (EC۳.۲.۱.۲۰, Saccharomyces cerevisiae) at ۲۰ U/mg concentration.  Results: Four compounds showed higher α-glucosidase inhibitory activity in comparison to a standard, i.e., Acarbose. Compound ۵q displays the most potent α-glucosidase inhibitory activity (IC۵۰ = ۱۵۵.۴ ± ۶.۰ μM).  Conclusion: In conclusion, some of the synthesized compounds, including heterocyclic core molecules, have shown remarkable activity that could be considered as subjects for the development of new, more efficient inhibitors of the α-glucosidase enzyme.

Keywords:

α-Glucosidase inhibitors , Pyrazolophthalazine , Malononitrile , Aldehyde