Discovery, Biological Evaluation and Binding Mode Investigation of Novel Butyrylcholinesterase Inhibitors Through Hybrid Virtual Screening.

ABSTRACT: Butyrylcholinesterase (BChE), plays a critical role in alleviating the symptoms of Alzheimer's disease (AD) by regulating acetylcholine levels, emerging as an attractive target for AD treatment. This study employed a quantitative structure-activity relationship (QSAR) model based on ECFP4 molecular fingerprints with several machine learning algorithms (XGBoost, RF, SVM, KNN), among which the XGBoost model showed the best performance (AUC = 0.9740). A hybrid strategy integrating ligand- and structure-based virtual screening identified 12 hits from the Topscience core database, three of which were identified for the first time. Among them, piboserod and Rotigotine demonstrated the best BChE inhibitory potency (IC₅₀ = 15.33 μM and 12.76 μM, respectively) and exhibited favorable saf

SUBMITTER: Li L 

PROVIDER: S-EPMC12113681 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature