University of Hertfordshire

Standard

The psychonauts’ benzodiazepines; quantitative structure-activity relationship (QSAR) analysis and docking prediction of their biological activity. / Catalani, Valeria; Botha, Michelle; Corkery, John Martin; Guirguis, Amira; Vento, Alessandro; Scherbaum, Norbert; Schifano, Fabrizio.

In: Pharmaceuticals, Vol. 14, No. 8, 720, 26.07.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{13248321bb374a3b95b8f6419a1a24ae,
title = "The psychonauts{\textquoteright} benzodiazepines; quantitative structure-activity relationship (QSAR) analysis and docking prediction of their biological activity",
abstract = "Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly re-ported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (e.g., quantita-tive structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder{\textregistered}) and to predict their possible activi-ty/affinity on the gamma-aminobutyric acid 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{\textregistered}. 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 im-portance 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 in-formation on biological activity for index novel DBZDs, as preliminary data for further investiga-tions.",
keywords = "Designer Benzodiazepines, QSAR, Docking, Web Crawler, Computational Models, MOE, NPSfinder{\textregistered}",
author = "Valeria Catalani and Michelle Botha and Corkery, {John Martin} and Amira Guirguis and Alessandro Vento and Norbert Scherbaum and Fabrizio Schifano",
note = "{\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).",
year = "2021",
month = jul,
day = "26",
doi = "10.3390/ph14080720",
language = "English",
volume = "14",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "MDPI",
number = "8",

}

RIS

TY - JOUR

T1 - The psychonauts’ benzodiazepines; quantitative structure-activity relationship (QSAR) analysis and docking prediction of their biological activity

AU - Catalani, Valeria

AU - Botha, Michelle

AU - Corkery, John Martin

AU - Guirguis, Amira

AU - Vento, Alessandro

AU - Scherbaum, Norbert

AU - Schifano, Fabrizio

N1 - © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PY - 2021/7/26

Y1 - 2021/7/26

N2 - Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly re-ported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (e.g., quantita-tive 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 activi-ty/affinity on the gamma-aminobutyric acid 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 im-portance 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 in-formation on biological activity for index novel DBZDs, as preliminary data for further investiga-tions.

AB - Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly re-ported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (e.g., quantita-tive 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 activi-ty/affinity on the gamma-aminobutyric acid 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 im-portance 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 in-formation on biological activity for index novel DBZDs, as preliminary data for further investiga-tions.

KW - Designer Benzodiazepines

KW - QSAR

KW - Docking

KW - Web Crawler

KW - Computational Models

KW - MOE

KW - NPSfinder®

U2 - 10.3390/ph14080720

DO - 10.3390/ph14080720

M3 - Article

VL - 14

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 8

M1 - 720

ER -