Abstract
To propose a plausible binding mode between piperine and derivatives inside acetylcholinesterase (AChE) by molecular docking simulations, which might explain the observed experimental inhibitory activity of the enzyme, the anticholinesterase activity of compounds was tested using a microplate- reader assay based on the Ellman method modified by Rhee. Docking simulations were performed with GOLD 4.1 program based on the binding mode between AChE and donepezil due to the structural similarity of this drug with piperine. Piperine, piperic acid, and piperic ester exhibit AChE in vitro inhibitory activity of 46.5, 50.6, and 63.6%, respectively. Docking simulations revealed favorable molecular interactions of these compounds within the hydrophobic binding pocket of AChE. Piperine and its derivatives seem to be a good starting point for developing novel acetylcholinesterase inhibitors with therapeutical potential in Alzheimer’s disease treatment.
Keywords: Acetylcholinesterase inhibitors, Alzheimer’s disease, ester synthetic derivatives, molecular docking, natural alkaloid, piperine.