Abstract
AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.