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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa57425
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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-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.
Keywords: designer benzodiazepines; QSAR; docking; web crawler; computational models; MOE; NPSfinder®
College: Swansea University Medical School
Issue: 8
Start Page: 720