Investigation of interaction of propolis flavonoid compounds with human acetylcholinesterase using molecular docking

vAcetylcholinesterase inhibitors (anticholinesterases) are commonly used to improve the symptoms of Alzheimer's disease and the other forms of dementia and central nervous system disorders. Propolis is a sticky resinous substance produced by honey bees and exhibits a variety of biological activities such as anticancer, antioxidant, antimicrobial and antifungal. Recently, a number of articles have been published on the anticholinesterase activity of propolis. In this study, the interaction of 17 propolis flavonoid compounds with human acetylcholinesterase (hAChE) was investigated using molecular docking. These studies were performed with AutoDock Vina software and the grid box was designed to be placed on the active site gorge of the enzyme. The results obtained showed that all these compounds bind to this region with very good binding energy (-7 to -8.9 kcal/mol). The highest and lowest binding energies are related to rutin and fisetin, respectively. Investigation of the amino acids involved in the interaction demonstrated that all of these compounds interact with PAS and acyl pocket. The two compounds, caffeic acid phenethyl ester (CAPE) and myricetin, also interact with CAS and oxyanion hole. Myricetin is the only compound that has the ability to bind to two amino acids belonging to the catalytic triad. The results of this study suggest that all of these flavonoid compounds have the ability to inhibit the hAChE activity by binding to the active site gorge of the enzyme and are therefore suitable candidates for further studies to design new anticholinesterase drugs.