Identification of BACE1 inhibitors for Alzheimer s disease using molecular docking method

Alzheimer’s disease (AD), is a neurodegenerative, progressive, and fatal disorder, is the leading cause of dementia threatening the elderly population [1]. BACE1, a candidate β-secretase enzyme, initiates the pathogenesis of Alzheimer s disease (AD) through the production of amyloid β peptide (Aβ), which serves as a potential therapeutic target [2]. The 3D structure of BACE1, with the PDB ID of 4IVS and resolution of 2.64 Å was retrieved from Protein Data Bank (www.rcsb.org). The natural isoprenylated coumarins including mesuol, and isomesuol were obtained from the PubChem server as 3D structures in SDF files. After validation, these compounds were investigated by docking studies and the compounds with best docking score have been selected. The binding energy and main interactions between the mesuol and isomesuol and BACE1 binding pocket were investigated in detail. The mesuol and isomesuol had a good capability to block the BACE1 with the binding affinity of -10.79 and -10.44 kcal/mol. In addition, these compounds passed Lipinski’s “rule of five”. These findings suggest that these compounds could be used for BACE1 inhibition in the Alzheimer’s disease, after more investigation.