Title:Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer’s Disease: An In-silico Study
Volume: 26
Issue: 37
Author(s): Shu Liu, Minyan Dang, Yan Lei, Syed S. Ahmad, Mohammad Khalid, Mohammad A. Kamal and Li Chen*
Affiliation:
- Department of Neurology, Shaanxi Provincial People’s Hospital, 256 friendship west road, BinLin, Xi’an, Shaanxi, 710068,China
Keywords:
Alzheimer's disease, AChE, BuChE, ajmalicine, binding energy, inhibition constant.
Abstract:
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.
