👤 Nongmaithem Randhoni Chanu

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in amyloid-β generation and remains an important target in Alzheimer's disease (AD) drug discovery. Here, we present NeuroBACE-ML, a reliability-aware screening framework for high-throughput prioritization of potent BACE1 inhibitors from small-molecule libraries. Human BACE1 bioactivity records were curated from ChEMBL and standardized on a pIC Show less

Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes. 8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions. The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology. 8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability. Show less