Aim: 2-Thioxothiazolidin-4-one represents a versatile scaffold in drug development. The authors used it to prepare new potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that can be utilized, e.g., to treat Alzheimer's disease. Materials & methods: 3-Amino-2-thioxothiazolidin-4-one was modified at the amino group or active methylene, using substituted benzaldehydes. The derivatives were evaluated for inhibition of AChE and BChE (Ellman's method). Results & conclusion: The derivatives were obtained with yields of 52-94%. They showed dual inhibition with IC50 values from 13.15 μM; many compounds were superior to rivastigmine. The structure-activity relationship favors nitrobenzylidene and 3,5-dihalogenosalicylidene scaffolds. AChE was inhibited noncompetitively, whereas BChE was inhibited with a mixed type of inhibition. Molecular docking provided insights into molecular interactions. Each enzyme is inhibited by a different binding mode.

Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice Studentská 573 532 10 Pardubice Czech Republic

Department of Chemistry Faculty of Science J E Purkinje University Pasteurova 3632 15 400 96 Ústí nad Labem Czech Republic

Department of Organic and Bioorganic Chemistry Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 500 03 Hradec Králové Czech Republic

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