A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50=1.3+/-0.01muM) and butyrylcholinesterase (IC50=1.2+/-0.09muM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57+/-0.01muM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Abeta1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu(2+)-induced Abeta1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Abeta1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.
        
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Bai P, Wang K, Zhang P, Shi J, Cheng X, Zhang Q, Zheng C, Cheng Y, Yang J, Lu X, Sang Z (2019) Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease Eur Journal of Medicinal Chemistry183: 111737
Bai P, Wang K, Zhang P, Shi J, Cheng X, Zhang Q, Zheng C, Cheng Y, Yang J, Lu X, Sang Z (2019) Eur Journal of Medicinal Chemistry183: 111737