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The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

Valeria Catalani, Michelle Botha, John Martin Corkery, Amira Guirguis Orcid Logo, Alessandro Vento, Norbert Scherbaum, Fabrizio Schifano

Pharmaceuticals, Volume: 14, Issue: 8, Start page: 720

Swansea University Author: Amira Guirguis Orcid Logo

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DOI (Published version): 10.3390/ph14080720

Abstract

Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activ...

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Published in: Pharmaceuticals
ISSN: 1424-8247
Published: MDPI AG 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa57425
first_indexed 2021-07-21T08:11:28Z
last_indexed 2022-05-21T03:30:54Z
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spelling 2022-05-20T11:05:01.3888450 v2 57425 2021-07-20 The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity b49270b9a0d580cf4f31f9a1b6c93f87 0000-0001-8255-0660 Amira Guirguis Amira Guirguis true false 2021-07-20 MEDS Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder®) and to predict their possible activity/affinity on the gamma-aminobutyric acid A receptors (GABA-ARs). The computational software MOE was used to calculate 2D QSAR models, perform docking studies on crystallised GABA-A receptors (6HUO, 6HUP) and generate pharmacophore queries from the docking conformational results. 101 DBZDs were identified online by NPSfinder®. The validated QSAR model predicted high biological activity values for 41% of these DBDZs. These predictions were supported by the docking studies (good binding affinity) and the pharmacophore modelling confirmed the importance of the presence and location of hydrophobic and polar functions identified by QSAR. This study confirms once again the importance of web-based analysis in the assessment of drug scenarios (DBZDs), and how computational models could be used to acquire fast and reliable information on biological activity for index novel DBZDs, as preliminary data for further investigations. Journal Article Pharmaceuticals 14 8 720 MDPI AG 1424-8247 designer benzodiazepines; QSAR; docking; web crawler; computational models; MOE; NPSfinder® 26 7 2021 2021-07-26 10.3390/ph14080720 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2022-05-20T11:05:01.3888450 2021-07-20T07:29:01.3087170 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Valeria Catalani 1 Michelle Botha 2 John Martin Corkery 3 Amira Guirguis 0000-0001-8255-0660 4 Alessandro Vento 5 Norbert Scherbaum 6 Fabrizio Schifano 7 57425__20684__328542c30d4a4a6bbb149d62a0e2e04a.pdf 57425.pdf 2021-08-19T16:50:16.7103017 Output 3548221 application/pdf Version of Record true Copyright: © 2021 by the authors. This is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license true eng https://creativecommons.org/licenses/by/4.0/
title The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
spellingShingle The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
Amira Guirguis
title_short The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
title_full The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
title_fullStr The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
title_full_unstemmed The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
title_sort The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
author_id_str_mv b49270b9a0d580cf4f31f9a1b6c93f87
author_id_fullname_str_mv b49270b9a0d580cf4f31f9a1b6c93f87_***_Amira Guirguis
author Amira Guirguis
author2 Valeria Catalani
Michelle Botha
John Martin Corkery
Amira Guirguis
Alessandro Vento
Norbert Scherbaum
Fabrizio Schifano
format Journal article
container_title Pharmaceuticals
container_volume 14
container_issue 8
container_start_page 720
publishDate 2021
institution Swansea University
issn 1424-8247
doi_str_mv 10.3390/ph14080720
publisher MDPI AG
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder®) and to predict their possible activity/affinity on the gamma-aminobutyric acid A receptors (GABA-ARs). The computational software MOE was used to calculate 2D QSAR models, perform docking studies on crystallised GABA-A receptors (6HUO, 6HUP) and generate pharmacophore queries from the docking conformational results. 101 DBZDs were identified online by NPSfinder®. The validated QSAR model predicted high biological activity values for 41% of these DBDZs. These predictions were supported by the docking studies (good binding affinity) and the pharmacophore modelling confirmed the importance of the presence and location of hydrophobic and polar functions identified by QSAR. This study confirms once again the importance of web-based analysis in the assessment of drug scenarios (DBZDs), and how computational models could be used to acquire fast and reliable information on biological activity for index novel DBZDs, as preliminary data for further investigations.
published_date 2021-07-26T20:03:36Z
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