SYNTHESIS AND INVESTIGATION OF ANTI-ACETYLCHOLINESTERASE ACTIVITY IN SILICO AND IN VITRO OF SOME CHALCONES

Abstract

Background: Alzheimer is a major cause of dementia in the elderly and acetylcholinesterase inhibitors are used to treat the symptoms of this disease. Recently, chalcones have been reported as potential acetylcholinesterase inhibitors. Materials and methods: In this study, Claisen-Schmidt condensation reaction was applied to synthesize chalcones. Anti-acetylcholinesterase activity of these chalcones was determined by Ellman method. Molecular docking studies on acetylcholinesterase were performed to explain the interaction between these chalcone analogues and acetylcholinesterase active site at molecular level. Results: A total of twenty chalcones were synthesized and determined for in vitro anti-acetylcholinesterase activity. The results indicated that six compounds having IC50 value below 100 µM, three compounds having IC50 value in the range of 100 µM and 300 µM, the rest having IC50 value above 300 µM. Chalcone S17 (4’-amino-2-chlorochalcone) shows the strongest anti-acetylcholinesterase activity in the investigated group with IC50 value of 36.10 µM. In combination with the results of the in vitro anti-acetylcholinesterase activity, molecular docking study is used to explain the interaction between chalcone molecules and their active site, and the structure-activity relationship is abstracted. Conclusions: Our study indicated that the 2’-hydroxychalcones with halogen functional groups on B ring are strong acetylcholinesterase inhibitors. Chalcone S17 (4’-amino-2-chlorochalcone) could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors. Keywords: acetylcholinesterase, AChE, Alzheimer, chalcon, docking. Key words: A cetylcholinesterase, AChE, Alzheimer, chalcon, docking