Synthesis of Novel Chalcones as Acetylcholinesterase Inhibitors

• Main Authors: Thanh-Dao Tran, Thi-Cam-Vi Nguyen, Ngoc-Son Nguyen, Dai-Minh Nguyen, Thi-Thu-Ha Nguyen, Minh-Tri Le, Khac-Minh Thai
• Format: Article
• Language: English
• Published: MDPI AG 2016-07-01
• Series: Applied Sciences
• Subjects: benzylaminochalcones; Claisen-Schmidt condensation; acetylcholinesterase; Ellman’s method; β-amyloid aggregation; docking
• Online Access: http://www.mdpi.com/2076-3417/6/7/198

A new series of benzylaminochalcone derivatives with different substituents on ring B were synthesized and evaluated as inhibitors of acetylcholinesterase. The study is aimed at identification of novel benzylaminochalcones capable of blocking acetylcholinesterase activity for further development of an approach to Alzheimer’s disease treatment. These compounds were produced in moderate to good yields via Claisen-Schmidt condensation and subjected to an in vitro acetylcholinesterase inhibition assay, using Ellman’s method. The in silico docking procedure was also employed to identify molecular interactions between the chalcone compounds and the enzyme. Compounds with ring B bearing pyridin-4-yl, 4-nitrophenyl, 4-chlorophenyl and 3,4-dimethoxyphenyl moieties were discovered to exhibit significant inhibitory activities against acetylcholinesterase, with IC50 values ranging from 23 to 39 µM. The molecular modeling studies are consistent with the hypothesis that benzylaminochalcones could exert their effects as dual-binding-site acetylcholinesterase inhibitors, which might simultaneously enhance cholinergic neurotransmission and inhibit β-amyloid aggregation through binding to both catalytic and peripheral sites of the enzyme. These derivatives could be further developed to provide novel leads for the discovery of new anti-Alzheimer drugs in the future.