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New 3-amino-2-thioxothiazolidin-4-one-based inhibitors of acetyl- and butyryl-cholinesterase: synthesis and activity.
Krátký, Martin; Novácková, Karolína; Svrcková, Katarína; Svarcová, Markéta; Stepánková, Sárka.
Afiliación
  • Krátký M; Department of Organic & Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.
  • Novácková K; Department of Organic & Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.
  • Svrcková K; Department of Biological & Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic.
  • Svarcová M; Department of Organic & Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.
  • Stepánková S; Department of Chemistry, Faculty of Science, J. E. Purkinje University, Pasteurova 3632/15, 400 96, Ústí nad Labem, Czech Republic.
Future Med Chem ; 16(1): 59-74, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38047370
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcolinesterasa / Butirilcolinesterasa / Inhibidores de la Colinesterasa Idioma: En Revista: Future Med Chem Año: 2024 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcolinesterasa / Butirilcolinesterasa / Inhibidores de la Colinesterasa Idioma: En Revista: Future Med Chem Año: 2024 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido