Acetylcholinesterase (AChE), one of the major therapeutic strategies for the treatment of Alzheimer's disease (AD) is to increase the acetylcholine (ACh) level in the brain by inhibiting the biological activity of AChE. In this present work, a set of alkaloids and flavonoids against AChE enzyme were screened by computational chemistry techniques. The docking results showed that among alkaloid compounds the oxindole alkaloid namely mitragynine oxidole B (MITOB) and the indole alkaloids namely mitragynine (MIT) exhibited a good binding affinity towards AChE. These two compounds were then studied by molecular dynamics (MD) simulations. The binding free energy calculation and ligand-protein binding pattern suggested that both alkaloids could interact with AChE very well. Since MIT is the main alkaloid constituent of Mytragyna speciose leaves, this compound was isolated from M. speciose leaves and tested for anti-AChE activity. As a result, the isolated MIT had an inhibitory activity with pIC50 value of 3.57. This finding provided that the mitragynine compound has the potential to be as a therapeutic agent for further anti-AChE drug development in treatment of Alzheimer's disease.
Keywords: Acetylcholinesterase; Alzheimer’s disease; Docking; M. speciosa; MD simulation; Mitragynine.