Potent acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, and docking study of acridone linked to 1,2,3-triazole derivatives

• DOI: 10.1016/j.ejmech.2015.01.044
• Publication Date: 2015-01-22T11:05:51Z
• Authors: Maryam Mohammadi-...; Mina Saeedi; Narges Shamsaei Z...; Mohammad Mahdavi; Reyhaneh Sabourian; Elahe Karimpour R...; Heshmatollah Alin...; Mahnaz Khanavi; Alireza Foroumadi; Abbas Shafiee; Tahmineh Akbarzadeh
• Keywords: Acridone; Butyrylcholinesterase; Docking (animal); Propargyl bromide; 1,2,3-Triazole; Propargyl; Alkyne; Triazole

A novel series of acridone linked to 1,2,3-triazole derivatives have been synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. The synthetic approach was started from the reaction of 2-bromobenzoic acid with aniline derivatives and subsequent cyclization reaction to give acridone derivatives. Then, reaction of the later compounds with propargyl bromide followed by azide-alkyne cycloaddition reaction (click reaction) led to the formation of the title compounds in good yields. Among the synthesized compounds, 10-((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methoxyacridin-9(10H)-one 9g, depicted the most potent anti-AChE activity (IC50 = 7.31 μM). Also, docking study confirmed the results obtained through in vitro experiments and predicted possible binding conformation.