WITHDRAWN: Pharmacological evaluation of 3-benzyloxyflavones for β-glucosidase inhibition: Experimental, kinetic and computational approaches.

β-Glucosidase is a crucial enzyme involved in carbohydrate metabolism, playing a key role in the hydrolysis of glycosidic bonds in dietary polysaccharides. Inhibition of β-glucosidase has emerged as a promising therapeutic strategy for managing postprandial hyperglycemia in diabetes by delaying/slowing glucose absorption and moderating blood sugar levels. In this study, a series of 3-benzyloxyflavone derivatives (1-10) was designed and, for the first time, evaluated for both in vitro and in vivo inhibitory activity against the β-glucosidase enzyme. The enzyme inhibitory potential of these derivatives was further assessed in an antihyperglycemic context using in vivo mechanism-based assays on p-nitrophenyl-β-D-glucopyranoside (PGLT) induced diabetic models. Additionally, structure-activity relationship (SAR) was employed to identify structural features crucial for activity. Molecular docking analyses revealed that both the potent compounds and co-crystallized ligands shared similar binding orientations within the active sites of β-glucosidase (PDB IDs: 3AJ7; 66K1). Molecular dynamics (MD) simulations validated the stability of the inhibitor-enzyme complexes under physiological conditions. Drug-likeness analysis was also conducted to assess the pharmacokinetic potential of the derivatives. We have also conducted Density Functional Theory (DFT) studies on the lead compounds to gain deeper insights into their electronic properties, structural stability, and interaction mechanisms with the target enzyme. The results highlighted several derivatives with significant inhibitory activity, desirable pharmacokinetic profiles, and promising drug-like properties, making them potential candidates for therapeutic development. The target derivatives (1-10) demonstrated strong potential as lead compounds for developing new anti-diabetic agents with effective anti-hyperglycemic properties.