Acetylcholinesterase (AChE) inhibitors are yet the best drugs currently available for the management of Alzheimer's disease. The recent phytochemical investigation has led to the isolation of a new depsidone 1 with moderate AChE activity (1 μg). This work was focused on its electronic properties analysed using commercially available programs. Both the active depsidone molecule 1 and galanthamine showed to have higher HOMO energies than the inactive depsidones 2-4, isolated from the same lichen species. However, the amino depsidone derivative 7, whose structure was proposed using computational approaches, is expected to be more active AChE inhibitor than the depsidone 1, due to the improved HOMO energy value. In addition, the molecular docking study indicated that the compound 7 has ability to make the well-known interactions of potent AChE inhibitors with the enzyme active site. The data presented herein support the design of novel AChE inhibitors based on the depsidone scaffold.
Keywords: AChE inhibitors; density functional theory; electronic properties; molecular docking.