Evaluation of Natural Flavonoid Compounds in Amyloid-β (Aβ) Inhibition for Alzheimer’s Disease Treatment

Alzheimer’s Disease (AD) is a complex neurodegenerative condition characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, resulting in significant cognitive impairment. Currently, two drugs have been approved for Alzheimer’s treatment, however, it does not specifically target the amyloid β (Aβ) plaques and neurofibrillary tangles (NFT). Given that, herbal remedies from plants have also been recommended to enhance cognitive function and alleviate AD symptoms. Therefore, this study aims to evaluate potential natural flavonoid compounds to target the inhibition of amyloid β as a novel treatment for AD, using an in silico structure-based approach. 3D structure of the amyloid β protein target and the flavonoid compounds are acquired from Protein Data Bank (PDB) and PubChem database, respectively. The flavonoids are first screened for drug-likeness by ADME (Absorption, Distribution, Metabolism, and Excretion) screening and toxicity prediction using SWISS-ADME and ProTox-II web server. Quantitative structure-activity relationship (QSAR) analysis is also done to check for amyloid beta aggregation inhibitors and beta-amyloid protein antagonist activity in the compounds. Molecular docking and visualization are done to analyze the binding affinity of the ligands to the protein target using CB-Dock2. Finally, we perform molecular dynamics using CABSFLEX2 web-server to predict the protein fluctuations based on the root mean square fluctuations (RMSF) of the best flavonoid compound. Based on the drug-likeness, toxicity, and QSAR analysis, epicatechin shows the best potential flavonoid compound as amyloid β inhibitor. Two poses were found for 1 2 epicatechin which had identical binding energies but different pocket sizes. Our findings indicate the potential for natural flavonoid compounds as an alternative treatment in AD targeting amyloid β plaques activity.