Exploring coumarin derivatives as promising Acetylcholinesrtage inhibitors in alzheimer disease: Integrating QSAR, docking, MD simulations, and DFT study

Alzheimer’s disease, a major health concern primarily distressing older population, remains without a cure, with current treatments providing only symptomatic relief. This study focused on identifying coumarin-based herbal molecules with potent activity against the Alzheimer’s disease. A 2D-QSAR model was generated to facilitate virtual screening, leading to the identification of three herbal molecules- Gallocatechin 3_O_gallate, Quercetin, and Lariciresinol with promising predicted biological activity. Subsequent molecular docking simulations shortlisted daidzein 4′-O-glucuronide, apigenin 7-O-rutinoside, and quercetin, all of them showed higher docking scores when compared to standard drug donepezil. Notably, Quercetin was identified as a hit in both QSAR- and docking-dependent virtual screening approaches. Molecular dynamics simulations further confirmed stability of interactions between these molecules and target receptor. These results indicate that Gallocatechin 3-O-gallate, lariciresinol, Daidzein 4′_O_glucuronide, Apigenin 7_O_rutinoside, and Quercetin have significant potential as lead compounds for the development of effective Alzheimer’s disease treatments.