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, Alessandro Vento, Norbert Scherbaum, Fabrizio Schifano

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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®) 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.
Original languageEnglish
Article number720
Number of pages19
JournalPharmaceuticals
Volume14
Issue number8
Early online date26 Jul 2021
DOIs
Publication statusE-pub ahead of print - 26 Jul 2021

Keywords

  • Designer Benzodiazepines
  • QSAR
  • Docking
  • Web Crawler
  • Computational Models
  • MOE
  • NPSfinder®

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