Virtual Screening of Anthranilic Acid-Based Alkaloids from Persicaria tinctoria as Inhibitors of Acetylcholinesterase

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, often linked to the dysfunction of acetylcholinesterase (AChE). In this study, anthranilic acid-based alkaloids isolated from Persicaria tinctoria were virtually screened for their inhibitory potential against AChE using molecular docking and molecular dynamics simulations. Docking analysis revealed that several compounds exhibited strong binding affinities, interacting with key residues at the catalytic active site, peripheral anionic site, and choline-binding site. Among them, Compound 13 demonstrated the highest binding affinity (–9.01 kcal/mol) and a favorable inhibition constant (253.32 nM), forming stable interactions with critical residues including TRP86, TYR124, TYR341, and PHE295. Molecular dynamics simulations confirmed the structural stability and flexibility of the AChE–Compound 13 complex, further supporting its potential as a lead candidate. Other compounds also showed varied inhibitory profiles, targeting peripheral and allosteric sites of the enzyme. These findings suggest that alkaloids from P. tinctoria may serve as promising natural scaffolds for developing novel AChE inhibitors for AD therapy.