Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer's Disease: An
AChE
Alzheimer's disease
BuChE
ajmalicine
binding energy
inhibition constant
Journal
Current pharmaceutical design
ISSN: 1873-4286
Titre abrégé: Curr Pharm Des
Pays: United Arab Emirates
ID NLM: 9602487
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
01
2020
accepted:
02
03
2020
pubmed:
9
4
2020
medline:
20
3
2021
entrez:
9
4
2020
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions. The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology. We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'. Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule. The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.
Sections du résumé
BACKGROUND
Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions.
OBJECTIVE
The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.
METHODS
We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'.
RESULTS
Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule.
CONCLUSION
The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.
Identifiants
pubmed: 32264807
pii: CPD-EPUB-105704
doi: 10.2174/1381612826666200407161842
doi:
Substances chimiques
Cholinesterase Inhibitors
0
Ligands
0
Secologanin Tryptamine Alkaloids
0
raubasine
4QJL8OX71Z
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4808-4814Informations de copyright
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