Virtual Screening of Polyphenolic Compounds from Edible Plants for Potential Application in Alzheimer’s Therapy

Abstract

Alzheimer’s disease is associated with reduced cholinergic neurotransmission, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a crucial therapeutic approach. This study used molecular docking to assess two reference inhibitors and two natural flavonoids against both enzymes. The reference inhibitor donepezil showed strong selectivity for AChE, while luteolin demonstrated balanced binding affinity and notable stability with both enzymes. Apigenin exhibited modest binding affinity for both targets, whereas rivastigmine showed the lowest binding affinity and inhibition potency. Energy analysis revealed that Van der Waals forces, hydrogen bonds, and desolvation mainly drive complex stabilization, with electrostatic effects playing a lesser role. The results emphasize luteolin’s potential as a dual AChE/BChE inhibitor and confirm donepezil’s selectivity for AChE. These insights support the rational design of new Alzheimer’s therapeutics, especially flavonoid-based compounds with optimized dual inhibition profiles.