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Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) as a complicated and progressive neurodegenerative disorder is the most common form of dementia and memory loss. On account of the multifactorial etiology of AD, the multi-target-directed ligand (MTDL) approach is a promising method in searching new drug candidates for this...

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Autores principales: Fereidoonnezhad, Masood, Mostoufi, Azar, Eskandari, Maryam, Zali, Samaneh, Aliyan, Fariba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269558/
https://www.ncbi.nlm.nih.gov/pubmed/30568682
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author Fereidoonnezhad, Masood
Mostoufi, Azar
Eskandari, Maryam
Zali, Samaneh
Aliyan, Fariba
author_facet Fereidoonnezhad, Masood
Mostoufi, Azar
Eskandari, Maryam
Zali, Samaneh
Aliyan, Fariba
author_sort Fereidoonnezhad, Masood
collection PubMed
description Alzheimer’s disease (AD) as a complicated and progressive neurodegenerative disorder is the most common form of dementia and memory loss. On account of the multifactorial etiology of AD, the multi-target-directed ligand (MTDL) approach is a promising method in searching new drug candidates for this disease. Here, in this paper more than 500 tacrine-coumarin hybrids have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate with less toxicity and better binding affinity than tacrine. The docking analysis was carried out using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS) and β-secretase (BACE1) (1W51) enzymes using AutoDock 4.2 and Vina. The promising results were obtained on the types of interactions. Based on docking on three targets and PLIF studies, the compounds that have better results were introduced as good candidates for synthesis. The validity of docking protocols was verified using a set of known active ligands and decoys on these targets.
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spelling pubmed-62695582018-12-19 Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease Fereidoonnezhad, Masood Mostoufi, Azar Eskandari, Maryam Zali, Samaneh Aliyan, Fariba Iran J Pharm Res Original Article Alzheimer’s disease (AD) as a complicated and progressive neurodegenerative disorder is the most common form of dementia and memory loss. On account of the multifactorial etiology of AD, the multi-target-directed ligand (MTDL) approach is a promising method in searching new drug candidates for this disease. Here, in this paper more than 500 tacrine-coumarin hybrids have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate with less toxicity and better binding affinity than tacrine. The docking analysis was carried out using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS) and β-secretase (BACE1) (1W51) enzymes using AutoDock 4.2 and Vina. The promising results were obtained on the types of interactions. Based on docking on three targets and PLIF studies, the compounds that have better results were introduced as good candidates for synthesis. The validity of docking protocols was verified using a set of known active ligands and decoys on these targets. Shaheed Beheshti University of Medical Sciences 2018 /pmc/articles/PMC6269558/ /pubmed/30568682 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Fereidoonnezhad, Masood
Mostoufi, Azar
Eskandari, Maryam
Zali, Samaneh
Aliyan, Fariba
Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title_full Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title_fullStr Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title_full_unstemmed Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title_short Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease
title_sort multitarget drug design, molecular docking and plif studies of novel tacrine−coumarin hybrids for the treatment of alzheimer’s disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269558/
https://www.ncbi.nlm.nih.gov/pubmed/30568682
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