In Silico Inhibition of BACE-1 by Selective Phytochemicals as Novel Potential Inhibitors: Molecular Docking and DFT Studies | Bentham Science

摘要

Background: Alzheimer’s Disease (AD) has become the most common age-dependent diseaseof dementia. The trademark pathologies of AD are the presence of amyloid aggregates in neurofibrils. Recentlyphytochemicals 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 literatureassessment. The ADMET studies, molecular docking and density functional theory (DFT) based analysiswere performed to analyze the potential inhibitory properties of these phytochemicals.Results: The ADMET and docking results exposed seven compounds that have high potential as aninhibitory agent against BACE-1 and show binding affinity >8.0 kcal/mol against BACE-1. They showbinding affinity greater than those of various previously reported inhibitors of BACE-1. Furthermore, DFTbased 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 comparedto 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 fromUncaria rhynchophylla i.e. 3a-dihydro-cadambine and another one was from VolvalerelactoneB fromplant Valeriana-officinalis. It is concluded that these phytochemicals are suitable candidates fordrug/inhibitor against BACE-1, and can be administered to humans after experimental validation throughin vitro and in vivo trials.