%0 Journal Article
%T Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer's Disease: An In-silico Study.
%A Liu S
%A Dang M
%A Lei Y
%A Ahmad SS
%A Khalid M
%A Kamal MA
%A Chen L
%J Curr Pharm Des
%V 26
%N 37
%D 2020
%M 32264807
%F 3.31
%R 10.2174/1381612826666200407161842
%X 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.<BR>The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.<BR>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'.<BR>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.<BR>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.