Shu Liu, Minyan Dang, Yan Lei, Syed S. Ahmad, Mohammad Khalid, Mohammad A. Kamal and Li Chen* Pages 4808 - 4814 ( 7 )
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.
Alzheimer's disease, AChE, BuChE, ajmalicine, binding energy, inhibition constant.
Department of Neurology, Tangshan Workers Hospital, Tangshan, Hebei, 063000, Innoscience Research Sdn Bhd, Jalan USJ 25/1, 47650 Subang Jaya, Selangor, Innoscience Research Sdn Bhd, Jalan USJ 25/1, 47650 Subang Jaya, Selangor, Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Department of Neurology, Shaanxi Provincial People’s Hospital, 256 friendship west road, BinLin, Xi’an, Shaanxi, 710068