2D-QSAR and molecular docking based virtual screening and molecular dynamic simulation of the indole based herbal molecules for the discovery of potent molecules in the treatment of Alzheimer's disease.

Alzheimer's disease, a significant health challenge predominantly affecting the elderly, currently lacks curative treatments, with existing therapies offering only symptomatic relief. This study aimed to identify herbal indole-based molecules with therapeutic potential against Alzheimer's disease. A 2D QSAR model was developed for virtual screening, identifying five promising herbal molecules with predicted biological activity. Molecular docking studies further narrowed the candidates to three molecules-Evodiamine, Hyrtinadine A, and Lyaloside-which exhibited superior docking scores compared to the standard drug Donepezil against Crystal Structure of Recombinant Human Acetylcholinesterase (PDB Id-4ey7). Molecular dynamics simulations validated the stability of these molecules' interactions with the target receptor. These findings suggest that Evodiamine, Hyrtinadine A, and Lyaloside hold potential as leads for developing effective treatments for Alzheimer's disease. Despite the encouraging insights obtained from the molecular docking and 2D-QSAR techniques, the study is constrained by the absence of in vitro and in vivo confirmation, requiring additional experimental assessments. To determine their therapeutic potential against Alzheimer's disease, future studies should concentrate on the pharmacokinetic profiles and preclinical evaluations of the identified lead compounds. Graphical abstract: Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00364-y.