Identification of novel pyrazole-containing thiazolidine-2,4-dione derivatives as potent α-glucosidase inhibitors: design, synthesis and antidiabetic assessment

In an effort to identify potent α-glucosidase inhibitors for the treatment of type 2 diabetes (T2DM), a series of hybrid pyrazole-containing thiazolidine-2,4-dione derivatives 10 (a-i) were synthesized, and evaluated for their α-glucosidase inhibitory activity. Furthermore, an in silico ADMET study validates passive GI absorption, whereas molecular docking and dynamics highlighted stable interactions with key residues between Receptor Proteins and the scaffold. Most of the synthesized compounds exhibited potent α-glucosidase inhibitory capability with IC₅₀ values ranging from 3.32 ± 1.27 to 25.58 ± 2.77 μM, compared to standard acarbose 69.89 ± 1.29 μM. Among synthesized compounds, 10e showed highest α-glucosidase inhibition by 21.05-fold higher than acarbose with moderate antioxidant activity. In vivo antihyperglycemic activity evaluation of compound 10e at doses 10 mg/kg and 50 mg/kg demonstrated a significant reduction in the blood glucose level in streptozotocin induced rats, thereby validating its T2DM action. Moreover, biochemical estimations showed that the levels of Alkaline Phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), urea, blood urea nitrogen and total protein restored to normal in 10e treatment group as compared to the diabetic group.