Mechanistic investigation on compounds from <i>Amorpha fruticosa</i> L. targeting acetylcholinesterase

Acetylcholinesterase (AChE) is the enzyme targeted by drugs used for the symptomatic treatment of cognitive decline associated with Alzheimer's disease. While <i>in vitro</i> data suggest the AChE inhibitory potential of <i>A. fruticosa</i> extracts and components such as rotenoids, in-depth mechanistic investigations are missing. A wide array of computational techniques, including ligand-based approaches, molecular docking, molecular dynamics, and machine learning-assisted toxicity prediction were enrolled in the current study, highlighting the rotenoid 6α,12α-dehydrodeguelin as a promising lead for the development of AChE inhibitors.