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Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation
For more than two decades, the development of potent acetylcholinesterase (AChE) inhibitors has been an ongoing task to treat dementia associated with Alzheimer’s disease and improve the pharmacokinetic properties of existing drugs. In the present study, we used three docking-based virtual screening...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833026/ https://www.ncbi.nlm.nih.gov/pubmed/33478277 http://dx.doi.org/10.1080/14756366.2021.1876685 |
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author | David, Benoit Schneider, Pascal Schäfer, Philipp Pietruszka, Jörg Gohlke, Holger |
author_facet | David, Benoit Schneider, Pascal Schäfer, Philipp Pietruszka, Jörg Gohlke, Holger |
author_sort | David, Benoit |
collection | PubMed |
description | For more than two decades, the development of potent acetylcholinesterase (AChE) inhibitors has been an ongoing task to treat dementia associated with Alzheimer’s disease and improve the pharmacokinetic properties of existing drugs. In the present study, we used three docking-based virtual screening approaches to screen both ZINC15 and MolPort databases for synthetic analogs of physostigmine and donepezil, two highly potent AChE inhibitors. We characterised the in vitro inhibitory concentration of 11 compounds, ranging from 14 to 985 μM. The most potent of these compounds, S-I 26, showed a fivefold improved inhibitory concentration in comparison to rivastigmine. Moderate inhibitors carrying novel scaffolds were identified and could be improved for the development of new classes of AChE inhibitors. |
format | Online Article Text |
id | pubmed-7833026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-78330262021-02-02 Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation David, Benoit Schneider, Pascal Schäfer, Philipp Pietruszka, Jörg Gohlke, Holger J Enzyme Inhib Med Chem Research Paper For more than two decades, the development of potent acetylcholinesterase (AChE) inhibitors has been an ongoing task to treat dementia associated with Alzheimer’s disease and improve the pharmacokinetic properties of existing drugs. In the present study, we used three docking-based virtual screening approaches to screen both ZINC15 and MolPort databases for synthetic analogs of physostigmine and donepezil, two highly potent AChE inhibitors. We characterised the in vitro inhibitory concentration of 11 compounds, ranging from 14 to 985 μM. The most potent of these compounds, S-I 26, showed a fivefold improved inhibitory concentration in comparison to rivastigmine. Moderate inhibitors carrying novel scaffolds were identified and could be improved for the development of new classes of AChE inhibitors. Taylor & Francis 2021-01-21 /pmc/articles/PMC7833026/ /pubmed/33478277 http://dx.doi.org/10.1080/14756366.2021.1876685 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper David, Benoit Schneider, Pascal Schäfer, Philipp Pietruszka, Jörg Gohlke, Holger Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title | Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title_full | Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title_fullStr | Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title_full_unstemmed | Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title_short | Discovery of new acetylcholinesterase inhibitors for Alzheimer’s disease: virtual screening and in vitro characterisation |
title_sort | discovery of new acetylcholinesterase inhibitors for alzheimer’s disease: virtual screening and in vitro characterisation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833026/ https://www.ncbi.nlm.nih.gov/pubmed/33478277 http://dx.doi.org/10.1080/14756366.2021.1876685 |
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