Investigation of <i>In-silico</i> DFT, ADMET Prediction and Molecular Docking Insight: Synthesis and <i>in-vitro</i> α-Amylase Activity of Novel Benzoxazole and Benzothiazole Scaffolds

In the search for novel antidiabetic agents, a series of benzoxazole and benzothiazole-based derivatives 5(a–f) and 6(a–f) were synthesized and evaluated for their inhibitory activity against [Formula: see text]-amylase, a key enzyme involved in carbohydrate metabolism. The synthesized compounds were characterized using spectroscopic techniques like 1 H-NMR, [Formula: see text]C-NMR and Mass analysis and their biological activity was assessed through in vitro [Formula: see text]-amylase inhibition assay. Several derivatives like 6c (8.20 ± 1.20 [Formula: see text]M), 5c (10.75 ± 2.34 [Formula: see text]M), 5f (12.60 ± 3.10 [Formula: see text]M) and 6a (13.18 ± 2.45 [Formula: see text]M) exhibited good inhibitory potency in comparison to standard drug acarbose (IC 50 [Formula: see text] 10.33 ± 1.10 [Formula: see text]M). Molecular docking studies were conducted to investigate the binding interactions of the active compounds with the [Formula: see text]-amylase active site, revealing strong hydrogen bonding and hydrophobic interactions with key catalytic residues. Furthermore, in silico pharmacokinetic profiling (ADME analysis) was performed to evaluate the drug-likeness and oral bioavailability of the selected candidates. The results indicated favorable pharmacokinetic properties for the most active compounds. This integrated experimental and computational study highlights the potential of benzoxazole and benzothiazole scaffolds as promising leads for the development of [Formula: see text]-amylase inhibitors for the treatment of type 2 diabetes mellitus.