Background: Alzheimer’s Disease (AD) has become the most common age-dependent disease
of dementia. The trademark pathologies of AD are the presence of amyloid aggregates in neurofibrils. Recently
phytochemicals being considered as potential inhibitors against various neurodegenerative, antifungal,
antibacterial and antiviral diseases in human beings.
Objective: This study targets the inhibition of BACE-1 by phytochemicals using in silico drug discovery analysis.
Methods: A total of 3150 phytochemicals were collected from almost 25 different plants through literature
assessment. The ADMET studies, molecular docking and density functional theory (DFT) based analysis
were performed to analyze the potential inhibitory properties of these phytochemicals.
Results: The ADMET and docking results exposed seven compounds that have high potential as an
inhibitory agent against BACE-1 and show binding affinity >8.0 kcal/mol against BACE-1. They show
binding affinity greater than those of various previously reported inhibitors of BACE-1. Furthermore, DFT
based analysis has shown high reactivity for these seven phytochemicals in the binding pocket of BACE-
1, based on ELUMO, EHOMO and Kohn-Sham energy gap. All seven phytochemicals were testified (as compared
to experimental ones) as novel inhibitors against BACE-1.
Conclusion: Out of seven phytochemicals, four were obtained from plant Glycyrrhiza glabra i.e. Shinflavanone,
Glabrolide, Glabrol and PrenyllicoflavoneA, one from Huperzia serrate i.e. Macleanine, one from
Uncaria rhynchophylla i.e. 3a-dihydro-cadambine and another one was from VolvalerelactoneB from
plant Valeriana-officinalis. It is concluded that these phytochemicals are suitable candidates for
drug/inhibitor against BACE-1, and can be administered to humans after experimental validation through
in vitro and in vivo trials.