Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors

New phenylisoxazole quinoxalin-2-amine hybrids were successfully synthesised with yields of 53–85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds , and exhibit great potential as α-glucosidase inhibitors, with being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of −8.9 ± 0.10 kcal mol−1, while compound exhibited the highest binding energy of −9.0 ± 0.20 kcal mol−1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.