Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer’s Disease: An In-silico Study

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Author(s): Shu Liu, Minyan Dang, Yan Lei, Syed Sayeed Ahmad, Mohammad Khalid, Mohammad A. Kamal, Li Chen*

Journal Name: Current Pharmaceutical Design

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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 noncognitive 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.

Keywords: Alzheimer's disease, AChE, BuChE, ajmalicine, binding energy, inhibition constant

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1381612826666200407161842
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