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ID: ALA4627271

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and evaluation of new 4-arylthiazole-2-amine derivatives as acetylcholinesterase inhibitors.

Authors: Xu Y, Jian MM, Han C, Yang K, Bai LG, Cao F, Ma ZY.

Abstract: A series of new 4-arylthiazole-2-amine derivatives as acetylcholinesterase inhibitors (AChEIs) were designed and synthesized, Furthermore, their inhibitory activities against acetylcholinesterase in vitro were tested by Ellman spectrophotometry, and the results of inhibitory activity test showed that most of them had a certain acetylcholinesterase inhibitory activity in vitro. Moreover, the IC50 value of compound 4f was to 0.66 μM, which was higher than that of Rivastigmine and Huperzine-A as reference compounds, and it had a weak inhibitory effect on butyrylcholinesterase. The potential binding mode of compound 4f with AChE was investigated by the molecular docking, and the results showed that 4f was strongly bound up with AChE with the optimal conformation, in addition, their binding energy reached -11.27 Kcal*mol-1. At last, in silico molecular property of the synthesized compounds were predicted by using Molinspiration online servers. It can be concluded that the lead AChEIs compound 4f presented satisfactory drug-like characteristics.

CiteXplore: 32008906

DOI: 10.1016/j.bmcl.2020.126985