Aurone-based α-glucosidase inhibitors for antidiabetic therapy: <i>in vitro</i>, <i>in vivo</i>, and <i>in silico</i> studies

This study aimed to evaluate the α-glucosidase inhibitory potential of newly synthesized aurone derivatives (1–14) using an integrated experimental and computational strategy, with emphasis on their antidiabetic potential. The compounds were evaluated through in vitro α-glucosidase inhibition and enzyme kinetic assays, along with in vivo studies to assess postprandial glucose control. Molecular docking, MM-GBSA calculations, and molecular dynamics (MD) simulations were performed to analyze interactions with diabetic targets (PDB IDs: 5NN4 and 6KK1). Furthermore, in silico ADME profiling and density functional theory (DFT) analyses were conducted to predict pharmacokinetic properties, drug-likeness, and electronic behavior. Several aurone derivatives exhibited strong α-glucosidase inhibition, surpassing standard drugs. Kinetic studies revealed a competitive inhibition mechanism, and in vivo evaluations confirmed their glucose-lowering effects – the first such report for aurones. Computational analyses indicated stable enzyme – ligand complexes with favorable binding affinities and ADME features. DFT results supported the observed structure – activity relationships and highlighted key electronic attributes influencing activity. This comprehensive study identifies aurones as potent α-glucosidase inhibitors with significant therapeutic potential, providing a strong foundation for further development of aurone-based antidiabetic agents.