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

Maryam  Hosseinpoor Tehrani; Seyed Ahmad Mirshokraie; Mehdi Khoobi; Mohsen Amini

doi:10.18502/pbr.v7i2.7365

Maryam Hosseinpoor Tehrani Department of chemistry, Payame Noor University (PNU), P.O Box 19395-4697, Tehran,Iran.
Seyed Ahmad Mirshokraie Department of chemistry, Payame Noor University (PNU), P.O Box 19395-4697, Tehran,Iran.
Mehdi Khoobi Department of Biomaterials, The Institue of Pharmaceutical Sciences(TIPS), Tehran University of Medical Sciences, Tehran, Iran.
Mohsen Amini Department of Medicinal Chemistry, Development Research Center, School of Pharmacy, and Drug Design, Tehran University of Medical Sciences, Tehran, Iran.

DOI: https://doi.org/10.18502/pbr.v7i2.7365

Keywords: α-Glucosidase inhibitors, Pyrazolophthalazine, Malononitrile, Aldehyde

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.