In Silico Inhibition of BACE-1 by Selective Phytochemicals as Novel Potential Inhibitors: Molecular Docking and DFT Studies.
Alzheimer Disease
/ drug therapy
Amyloid Precursor Protein Secretases
/ antagonists & inhibitors
Aspartic Acid Endopeptidases
/ antagonists & inhibitors
Binding Sites
/ drug effects
Drug Discovery
/ methods
Glycyrrhiza
/ chemistry
Humans
Lycopodiaceae
/ chemistry
Molecular Docking Simulation
Phytochemicals
/ pharmacology
Phytotherapy
/ methods
Valerian
/ chemistry
ADMET
BACE-1
DFT
Molecular Docking
in silico inhibition
phytochemicals
Journal
Current drug discovery technologies
ISSN: 1875-6220
Titre abrégé: Curr Drug Discov Technol
Pays: United Arab Emirates
ID NLM: 101157212
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
11
2018
revised:
16
01
2019
accepted:
31
01
2019
pubmed:
16
2
2019
medline:
21
9
2021
entrez:
16
2
2019
Statut:
ppublish
Résumé
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. This study targets the inhibition of BACE-1 by phytochemicals using in silico drug discovery analysis. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30767744
pii: CDDT-EPUB-96664
doi: 10.2174/1570163816666190214161825
doi:
Substances chimiques
Phytochemicals
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Aspartic Acid Endopeptidases
EC 3.4.23.-
BACE1 protein, human
EC 3.4.23.46
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-411Informations de copyright
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