Discovery of Novel Pyrrolidine-Based Chalcones as Dual Inhibitors of α-Amylase and α-Glucosidase: Synthesis, Molecular Docking, ADMET Profiles, and Pharmacological Screening

A series of chalcones containing a pyrrolidine moiety were synthesized to examine their in vitro α-amylase and α-glucosidase inhibitory activities, for the treatment of Diabetes mellitus, which is one of the most dangerous and rapidly increasing disorders of today. Compound 3 exhibited an excellent dual inhibitory effect with an IC50 value of 14.61 ± 0.12 μM against α-amylase, and with an IC50: 25.38 ± 2.09 μM against α-glucosidase. The in vitro cytotoxic effects of all compounds against nonsmall lung cancer (A549) and bronchial epithelial normal (BEAS-2B) cell lines were also evaluated. Compound 5 (IC50: 82.20 μM) and compound 8 (IC50: 59.96 μM) showed better cytotoxic activity than cisplatin against A549 (IC50: 84.39 μM) cells. Furthermore, these compounds had no harmful effect on healthy BEAS-2B cells at the determined IC50 values. Moreover, the molecular docking and molecular dynamics simulation analysis revealed that all synthesized compounds exhibited stronger binding affinities toward α-glucosidase and α-amylase compared to the positive control acarbose.