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In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening
Purpose: In this review, a set of aryl halides analogs were identified as potent checkpoint kinase 1 (Chk1) inhibitors through a series of computer-aided drug design processes, to develop models with good predictive ability, highlight the important interactions between the ligand and the Chk1 recept...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Tabriz University of Medical Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468235/ https://www.ncbi.nlm.nih.gov/pubmed/31011562 http://dx.doi.org/10.15171/apb.2019.011 |
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author | Ghaleb, Adib Aouidate, Adnane Bouachrine, Mohammed Lakhlifi, Tahar Sbai, Abdelouhid |
author_facet | Ghaleb, Adib Aouidate, Adnane Bouachrine, Mohammed Lakhlifi, Tahar Sbai, Abdelouhid |
author_sort | Ghaleb, Adib |
collection | PubMed |
description | Purpose: In this review, a set of aryl halides analogs were identified as potent checkpoint kinase 1 (Chk1) inhibitors through a series of computer-aided drug design processes, to develop models with good predictive ability, highlight the important interactions between the ligand and the Chk1 receptor protein and determine properties of the new proposed drugs as Chk1 inhibitors agents. Methods: Three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) approaches are used to determine structure activity relationship and confirm the stable conformation on the receptor pocket. Results: The statistical analysis results of comparative -molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models that employed for a training set of 24 compounds gives reliable values of Q(2) (0.70 and 0.94, respectively) and R(2) (0.68 and 0.96, respectively). Conclusion: Computer–aided drug design tools used to develop models that possess good predictive ability, and to determine the stability of the observed and predicted molecules in the receptor pocket, also in silico of pharmacokinetic (ADMET) results shows good properties and bioavailability for these new proposed Chk1 inhibitors agents. |
format | Online Article Text |
id | pubmed-6468235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Tabriz University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-64682352019-04-22 In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening Ghaleb, Adib Aouidate, Adnane Bouachrine, Mohammed Lakhlifi, Tahar Sbai, Abdelouhid Adv Pharm Bull Research Article Purpose: In this review, a set of aryl halides analogs were identified as potent checkpoint kinase 1 (Chk1) inhibitors through a series of computer-aided drug design processes, to develop models with good predictive ability, highlight the important interactions between the ligand and the Chk1 receptor protein and determine properties of the new proposed drugs as Chk1 inhibitors agents. Methods: Three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) approaches are used to determine structure activity relationship and confirm the stable conformation on the receptor pocket. Results: The statistical analysis results of comparative -molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models that employed for a training set of 24 compounds gives reliable values of Q(2) (0.70 and 0.94, respectively) and R(2) (0.68 and 0.96, respectively). Conclusion: Computer–aided drug design tools used to develop models that possess good predictive ability, and to determine the stability of the observed and predicted molecules in the receptor pocket, also in silico of pharmacokinetic (ADMET) results shows good properties and bioavailability for these new proposed Chk1 inhibitors agents. Tabriz University of Medical Sciences 2019-02 2019-02-21 /pmc/articles/PMC6468235/ /pubmed/31011562 http://dx.doi.org/10.15171/apb.2019.011 Text en ©2019 The Authors. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. |
spellingShingle | Research Article Ghaleb, Adib Aouidate, Adnane Bouachrine, Mohammed Lakhlifi, Tahar Sbai, Abdelouhid In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title | In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title_full | In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title_fullStr | In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title_full_unstemmed | In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title_short | In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening |
title_sort | in silico exploration of aryl halides analogues as checkpoint kinase 1 inhibitors by using 3d qsar, molecular docking study, and admet screening |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468235/ https://www.ncbi.nlm.nih.gov/pubmed/31011562 http://dx.doi.org/10.15171/apb.2019.011 |
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