A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)
The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2117912 |
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| author | Tereza Cristina Santos Evangelista Óscar López Adrián Puerta Miguel X. Fernandes Sabrina Baptista Ferreira José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck |
| author_facet | Tereza Cristina Santos Evangelista Óscar López Adrián Puerta Miguel X. Fernandes Sabrina Baptista Ferreira José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck |
| author_sort | Tereza Cristina Santos Evangelista |
| collection | DOAJ |
| description | The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC50 = 7–50 µM). For the most potent inhibitor of BuChE, Cornish-Bowden plots were used, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitor demonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheral anionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different as the benzotriazole moiety is accommodated in the catalytic anionic site. |
| format | Article |
| id | doaj-art-ab088dcc1fde417ebcc32bdfc2fb0a36 |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-ab088dcc1fde417ebcc32bdfc2fb0a362025-08-20T03:22:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712395240210.1080/14756366.2022.2117912A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)Tereza Cristina Santos Evangelista0Óscar López1Adrián Puerta2Miguel X. Fernandes3Sabrina Baptista Ferreira4José M. Padrón5José G. Fernández-Bolaños6Magne O. Sydnes7Emil Lindbäck8Department 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, La Laguna, SpainBioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, La Laguna, SpainDepartment of Organic Chemistry, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilBioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, 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 synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC50 = 7–50 µM). For the most potent inhibitor of BuChE, Cornish-Bowden plots were used, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitor demonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheral anionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different as the benzotriazole moiety is accommodated in the catalytic anionic site.https://www.tandfonline.com/doi/10.1080/14756366.2022.2117912IminosugarsInhibitorsCholinesterasesAlzheimer’s disease |
| spellingShingle | Tereza Cristina Santos Evangelista Óscar López Adrián Puerta Miguel X. Fernandes Sabrina Baptista Ferreira José M. Padrón José G. Fernández-Bolaños Magne O. Sydnes Emil Lindbäck A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) Journal of Enzyme Inhibition and Medicinal Chemistry Iminosugars Inhibitors Cholinesterases Alzheimer’s disease |
| title | A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) |
| title_full | A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) |
| title_fullStr | A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) |
| title_full_unstemmed | A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) |
| title_short | A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) |
| title_sort | hybrid of 1 deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase buche over acetylcholinesterase ache |
| topic | Iminosugars Inhibitors Cholinesterases Alzheimer’s disease |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2117912 |
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