Jesaconitine from Aconitum Species as a Potential Acetylcholinesterase Inhibitor: An in Silico Docking Study for Alzheimer’s Disease Management

Abstract

Background & Objectives: One of the established pharmacological strategies forslowing the progression of Alzheimer’s disease (AD) involves the inhibition of theacetylcholinesterase (AChE) enzyme. Current research has increasingly focused onthe identification of novel compounds, particularly naturally derived metabolites, thatexhibit potent modulatory activity alongside favorable toxicological profiles. In thiscontext, diterpenoid alkaloids represent a promising therapeutic class for modulating ADpathology through AChE inhibition.

Material & Methods: In this in silico study, molecular docking analyses were performedto screen and characterize diterpenoid alkaloids with the potential to attenuate ADprogression.

Results: Jesaconitine demonstrated a binding affinity of −6.72 kcal/mol, surpassing thatof the reference inhibitor Tacrine (−6.21 kcal/mol). Docking simulations revealed criticalinteractions within the active site of AChE, including conventional hydrogen-bondingnetworks involving the residues Ser125, Asn87, and Tyr337.

Conclusion: The findings of the present study identify Jesaconitine as a promising leadcompound for the management of AD through AChE inhibition, based on in silico dockingpredictions. Moreover, these results provide a theoretical framework for the developmentof novel AChE inhibitors and indicate that Jesaconitine warrants further experimental andpharmacological investigation.