Synthesis of Pyrazolo[1,2-b]phthalazine-5,10- dione Derivatives: A New Class of α –Glucosidase Inhibitors

Abstract

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[1,2-b]phthalazine-5,10-dione derivatives 5a–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 (EC3.2.1.20, Saccharomyces cerevisiae) at 20 U/mg concentration.
 Results: Four compounds showed higher α-glucosidase inhibitory activity in comparison to a standard, i.e., Acarbose. Compound 5q displays the most potent α-glucosidase inhibitory activity (IC50 = 155.4 ± 6.0 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.

Phthalic anhydride (PA): a valuable substrate in organic transformations

“…The route A afforded the phthalazines (215) possessing a direct Ar-Ar linkage. Route B provided the Lchloro-4-benzylphthalazine (219). The neat condensation between (215, 219) and selected phenols (135) resulted in the decomposition of the reaction mixtures.…”

“…The results revealed that some of the products are efficient inhibitors of the a-glucosidase enzyme compared to the acarbose standard. 219 (F) Lingampalle's group in 2019 constructed (252) though the domino reaction, in which, rstly, equal molar ratio of PA (1) and monohydrate hydrazine (56) were mixed at 80 °C for 15 min. Then, aromatic aldehydes (19) and malononitrile (48) were added and heated at 100 °C under microwave irradiation (300 W) for 10-16 min in the presence of boric acid (10 mol%) catalyst, which led to the corresponding adducts ( 252) with 86-94% yield.…”