In Silico Molecular Docking Studies of Phytoconstituents Identified in Curcuma zedoaria Rosc. on Acetylcholinesterase: An Enzyme Target for Anti Alzheimer’s Activity

Arumugam Madeswaran; Lakshmi Menon

Abstract

Alzheimer’s disease (AD) is a chronic, progressive and disabling organic brain disorder characterized by disturbances of multiple cortical functions. Acetylcholinesterase (AChE) inhibition is thought to be a promising approach towards the treatment of AD. The aim and objective of the present study is to perform in-silico docking analysis of the major active constituents identified in Curcuma zedoaria Rosc. against AChE for anti-Alzheimer’s activity. In this perspective, phytoconstituents like bisdemethoxy curcumin, curcumenone, curcuminolide-A, curcuminolide-B, demethoxy curcumin, eucalyptol and zingiberene were selected for the present study. Rivastigmine, a known AChE inhibitor was used as the standard. In-silico docking analysis was performed by using AutoDock 4.2 using Lamarckian genetic algorithm. The crystal structure of AChE (2WLS) was retrieved from brookhaeven protein data bank in pdb format. In the docking studies, docking parameters such as binding energy, inhibition constant and intermolecular energy were determined using AutoDock 4.2. Docking results of the selected phytoconstituents showed binding energy ranging between -5.47 and -8.04 kcal/mol when compared with that of the standard (-6.73 kcal/mol). Inhibition constant (98.31 to 1.28 μM) and intermolecular energy (-7.85 to -8.34 kcal/mol) of the phytoconstituents also coincide with the binding energy. These results clearly indicate that the phytoconstituents, especially, curcuminolide-A, curcuminolide-B and curcumenone have excellent binding sites and interactions with AChE compared to the standard. Further investigations on these compounds and in vivo studies are necessary to develop potential chemical entities in the management of Alzheimer’s disease.Keywords: Acetylcholinesterase, binding energy, inhibition constant, phytoconstituents, curcuminolide, AutoDockCite this ArticleArumu gam Madeswaran, Lakshmi Menon .In Silico Molecular Docking Studies ofPhytoconstituents Identified in Curcumazedoaria Rosc. on Acetylcholinesterase:An Enzyme Target for Anti Alzheimer’sActivity Research & Reviews: Journal ofComputational Biology. 2019; 8(3): 9 14 p.