Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers
| Autor: | I. Caroline Vaaland, Óscar López, Adrián Puerta, Miguel X. Fernandes, José M. Padrón, José G. Fernández-Bolaños, Magne O. Sydnes, Emil Lindbäck |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry. 38:349-360 |
| ISSN: | 1475-6374 1475-6366 |
| DOI: | 10.1080/14756366.2022.2150762 |
| Popis: | The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH2 groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC50 = 9.7 nM and 11 nM) and BuChE (IC50 = 8.1 nM and 9.1 nM). AChE exhibited the highest enantioselectivity (ca. 4-fold). The enantiomeric pairs of the heterodimers were found to be inactive (GI50 > 100 µM), or to have weak antiproliferative properties (GI50 = 84–97 µM) against a panel of human cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|