Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers
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,...
| Published in: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2150762 |
| _version_ | 1850041795630596096 |
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| author | I. Caroline Vaaland Óscar López Adrián Puerta Miguel X. Fernandes José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck |
| author_facet | I. Caroline Vaaland Óscar López Adrián Puerta Miguel X. Fernandes José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck |
| author_sort | I. Caroline Vaaland |
| collection | DOAJ |
| container_title | Journal of Enzyme Inhibition and Medicinal Chemistry |
| description | 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. |
| format | Article |
| id | doaj-art-d1237b9cbbfb410ca4a715968aec2873 |
| institution | Directory of Open Access Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| spelling | doaj-art-d1237b9cbbfb410ca4a715968aec28732025-08-20T00:31:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138134936010.1080/14756366.2022.2150762Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimersI. Caroline Vaaland0Óscar López1Adrián Puerta2Miguel X. Fernandes3José M. Padrón4José G. Fernández-Bolaños5Magne O. Sydnes6Emil Lindbäck7Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, NorwayDepartamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Seville, SpainBioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez, La Laguna, SpainBioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez, La Laguna, SpainBioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez, La Laguna, SpainDepartamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Seville, SpainDepartment of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, NorwayThe 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.https://www.tandfonline.com/doi/10.1080/14756366.2022.2150762CholinesterasesinhibitorsenantiomersmodellingAlzheimer’s disease |
| spellingShingle | I. Caroline Vaaland Óscar López Adrián Puerta Miguel X. Fernandes José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers Cholinesterases inhibitors enantiomers modelling Alzheimer’s disease |
| title | Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers |
| title_full | Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers |
| title_fullStr | Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers |
| title_full_unstemmed | Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers |
| title_short | Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers |
| title_sort | investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine iminosugar heterodimers |
| topic | Cholinesterases inhibitors enantiomers modelling Alzheimer’s disease |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2150762 |
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