Development of Oxazine-Based Hybrids as Inhibitors of α-Amylase, α-Glucosidase, Acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE) Enzymes, and Potential Therapeutics for Diabetes, Alzheimer's Disease, and Oxidative Stress

Oxazin-4-one-based synthetic derivatives (1–30) were evaluated for inhibitory activity against α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The molecules demonstrated potent inhibition, with IC₅₀ values of 18.65 ± 0.23 µM to 37.70 ± 0.06 µM for α-amylase and 15.68 ± 0.36 to 37.47 ± 0.13 µM for α-glucosidase, comparable to the reference drug acarbose (IC₅₀ = 16.98 ± 0.12 µM and 14.19 ± 0.06 µM, respectively). Antioxidant capacity was quantified using DPPH and ABTS radical scavenging assays. Kinetic analysis identified competitive and mixed-type inhibition mechanisms, while molecular docking simulations characterized the binding interactions within the active sites. Overall, these findings suggest that oxazin-4-one derivatives may serve as promising multitarget starting points for further optimization toward metabolic, neurodegenerative, and oxidative-stress-related pathways.