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Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank
Alzheimer's disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acety...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317581/ https://www.ncbi.nlm.nih.gov/pubmed/25685814 http://dx.doi.org/10.1155/2015/870389 |
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author | Nogara, Pablo Andrei Saraiva, Rogério de Aquino Caeran Bueno, Diones Lissner, Lílian Juliana Lenz Dalla Corte, Cristiane Braga, Marcos M. Rosemberg, Denis Broock Rocha, João Batista Teixeira |
author_facet | Nogara, Pablo Andrei Saraiva, Rogério de Aquino Caeran Bueno, Diones Lissner, Lílian Juliana Lenz Dalla Corte, Cristiane Braga, Marcos M. Rosemberg, Denis Broock Rocha, João Batista Teixeira |
author_sort | Nogara, Pablo Andrei |
collection | PubMed |
description | Alzheimer's disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski's rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC(50) value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) from Equus ferus (EfBChE), with IC(50) ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms. |
format | Online Article Text |
id | pubmed-4317581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-43175812015-02-15 Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank Nogara, Pablo Andrei Saraiva, Rogério de Aquino Caeran Bueno, Diones Lissner, Lílian Juliana Lenz Dalla Corte, Cristiane Braga, Marcos M. Rosemberg, Denis Broock Rocha, João Batista Teixeira Biomed Res Int Research Article Alzheimer's disease (AD) is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh) in the brain by using acetylcholinesterase inhibitors (AChEIs). In this study, we used the ZINC databank and the Lipinski's rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1) aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE) activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC(50) value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE) from Equus ferus (EfBChE), with IC(50) ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms. Hindawi Publishing Corporation 2015 2015-01-22 /pmc/articles/PMC4317581/ /pubmed/25685814 http://dx.doi.org/10.1155/2015/870389 Text en Copyright © 2015 Pablo Andrei Nogara et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Nogara, Pablo Andrei Saraiva, Rogério de Aquino Caeran Bueno, Diones Lissner, Lílian Juliana Lenz Dalla Corte, Cristiane Braga, Marcos M. Rosemberg, Denis Broock Rocha, João Batista Teixeira Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title | Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title_full | Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title_fullStr | Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title_full_unstemmed | Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title_short | Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski's Rule of Five and ZINC Databank |
title_sort | virtual screening of acetylcholinesterase inhibitors using the lipinski's rule of five and zinc databank |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317581/ https://www.ncbi.nlm.nih.gov/pubmed/25685814 http://dx.doi.org/10.1155/2015/870389 |
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