Synthesis of Pyrrolidine-Appended Quinolines as Dual Inhibitors for α-Glucosidaseand α-Amylase

In this work, we investigated the ability of pyrrolidine-appended quinoline derivatives to inhibit αamylase and α-glucosidase, two important targets for the treatment of type 2 diabetes. Compounds 4a-c were synthesized using two bioactive pharmacophores, 1-(2-chloroacetyl)pyrrolidine-2-carbonitrile 2 and substituted quinolines, and were subsequently characterized. Using acarbose as a standard, the compounds were evaluated for their ability to inhibit α-glucosidase and α-amylase. A detailed in silico analysis, including density functional theory (DFT) studies, molecular docking, and molecular dynamics simulations, was carried out to supplement the experimental results. According to the findings, compound 4b demonstrated encouraging in vitro inhibitory activity against α-glucosidase (IC50 = 41.06 ± 1.73 µg/mL) and α-amylase (IC50 = 22.84 ± 0.32 µg/mL), and was slightly less potent than acarbose, indicating its potential as a dual inhibitor. The compound can be further optimized and developed for clinical applications.