BACE1 and cholinesterase inhibitory activities of compounds from Cajanus cajan and Citrus reticulata: an in silico study.

Alzheimer's disease (AD) is one of the major neurodegenerative diseases whose underlying risk factors are yet to be fully understood. However, reduced cellular level of cholinesterase, as well as formation and deposition of amyloid plaques (Aβ) are thought to play critical roles in the pathogenesis of AD. Therefore, increases in cholinergic transmitter levels via cholinesterase (ChE) inhibitors as well as inhibition of amyloid plaques formation and aggregation via beta secretase-1 (BACE1) inhibitors have been proposed as treatment for this disease. This study was aimed at investigating the BACE1 and ChE inhibitory properties of compounds from Cajanus cajan and Citrus reticulata based on their traditional connection with the management of neurodegenerative diseases, coupled with their protective effects on chemical-induced cognitive impairment. Using in silico methods, one hundred and nineteen compounds from C. cajan and C. reticulata were docked with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1 using Vina. Molecular interactions of the top-ranked compounds for the 3 protein targets were viewed with Discovery Studio, followed by characterization of their ADME properties using the Swiss online ADME web tool. Among the one hundred and ninety nine compounds screened, 3 compounds, genistin (76), naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester (94) and vitexin (119) have remarkable binding affinity for the three protein targets and passed the oral drugability test, while only naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester (94) exhibited BBB permeation property. Genistin and vitexin from C. cajan and naphthalen-2-yl-acetic acid, 6-hydroxy-6-methyl-cyclodecyl ester from C. reticulata possibly contributed, at least in part, to the neurotherapeutic potentials of these plants.