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

Background & Objectives: One of the established pharmacological strategies for slowing the progression of Alzheimer’s disease (AD) involves the inhibition of the acetylcholinesterase (AChE) enzyme. Current research has increasingly focused on the identification of novel compounds, particularly naturally derived metabolites, that exhibit potent modulatory activity alongside favorable toxicological profiles. In this context, diterpenoid alkaloids represent a promising therapeutic class for modulating AD pathology through AChE inhibition. Material & Methods: In this in silico study, molecular docking analyses were performed to screen and characterize diterpenoid alkaloids with the potential to attenuate AD progression. Results: Jesaconitine demonstrated a binding affinity of −۶.۷۲ kcal/mol, surpassing that of the reference inhibitor Tacrine (−۶.۲۱ kcal/mol). Docking simulations revealed critical interactions within the active site of AChE, including conventional hydrogen-bonding networks involving the residues Ser۱۲۵, Asn۸۷, and Tyr۳۳۷. Conclusion: The findings of the present study identify Jesaconitine as a promising lead compound for the management of AD through AChE inhibition, based on in silico docking predictions. Moreover, these results provide a theoretical framework for the development of novel AChE inhibitors and indicate that Jesaconitine warrants further experimental and pharmacological investigation.

کلیدواژه ها:

Acetylcholinesterase ، Jesaconitine ، Diterpene alkaloid ، Molecular docking ، Alzheimer's disease