Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide

Bushra Waheed; Syed Muhammad Mukarram Shah; Fida Hussain; Mohammad Ijaz Khan; Anwar Zeb; Muhammad Saeed Jan

doi:10.1155/2022/1445604

Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide

Evid Based Complement Alternat Med. 2022 Mar 28:2022:1445604. doi: 10.1155/2022/1445604. eCollection 2022.

Authors

Bushra Waheed¹, Syed Muhammad Mukarram Shah¹, Fida Hussain¹, Mohammad Ijaz Khan¹, Anwar Zeb¹, Muhammad Saeed Jan¹

Affiliation

¹ Department of Pharmacy, University of Swabi, Swabi, KP, Pakistan.

Abstract

The prevalence of diabetes mellitus is persistently increasing globally creating a serious public health affliction. Diabetes mellitus is categorized into two major types designated as type I and Type II. Type I diabetes mellitus is characterized by complete lack of secretion of insulin, while Type II diabetes mellitus is the resistance of peripheral tissues to the action of insulin and inadequate compensatory secretion of insulin. Chronic hyperglycemia associated with diabetes causes failure of cardiovascular system, nervous system, kidneys, and eyes. At present, different types of drugs are used for the management of diabetes, but each of them is associated with more or less serious side effects. Therefore, we need to develop new therapeutic agents that have better efficacy and safety profile. In this study, three ketone derivatives of succinimides were synthesized based on Michael addition and characterized using NMR. All the synthesized compounds were checked for their in vitro α-amylase and α-glucosidase inhibitory activities. Further the synthesized compounds were also explored for their antioxidant activities, i.e, DPPH and ABTS assays. Based on the in vitro results, the synthesized compounds were further evaluated for in vivo antidiabetic activity. The synthesized compounds were (2-oxocyclohexyl)-1-phenylpyrrolidine-2,5-dione (BW1), benzyl-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW2), and (4-bromophenyl)-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW3). BW1 showed the highest inhibitory activity for DPPH causing 83.03 ± 0.48 at 500 μg/ml with IC₅₀ value of 10.84 μg/ml and highest inhibitory activity for ABTS causing 78.35 ± 0.23 at 500 μg/ml with IC₅₀ value of 9.40 μg/ml against ascorbic acid used as standard. BW1 also exhibited the highest activity against α-amylase and α-glucosidase inhibition causing 81.60 ± 0.00 at concentrations of 500 μg/ml with IC₅₀ value of 13.90 μg/ml and 89.08 ± 1.04 at concentrations of 500 μg/ml with IC₅₀ value of 10.49 μg/ml, respectively, against the standard drug acarbose.