Comparative assessment of some benzodiazepine drugs based on Density Functional Theory, molecular docking, and ADMET studies
Open Access
- 31 December 2021
- journal article
- Published by European Journal of Chemistry in European Journal of Chemistry
- Vol. 12 (4), 412-418
- https://doi.org/10.5155/eurjchem.12.4.412-418.2135
Abstract
Benzodiazepines are widely used to treat anxiety, insomnia, agitation, seizures, and muscle spasms. It works through the GABAA receptors to promote sleep by inhibiting brainstem monoaminergic arousal pathways. It is safe and effective for short-term use, and arises some crucial side effects based on dose and physical condition. In this investigation, physicochemical properties, molecular docking, and ADMET properties have been studied. Density functional theory with B3LYP/6-311G+(d,p) level of theory was set for geometry optimization and elucidate their thermodynamic, orbital, dipole moment, and electrostatic potential properties. Molecular docking and interaction calculations have performed against human GABAA receptor protein (PDB ID: 4COF) to search the binding affinity and effective interactions of drugs with the receptor protein. ADMET prediction has performed to investigate their absorption, metabolism, and toxic properties. Thermochemical data suggest the thermal stability; the docking result predicts effecting bindings and ADMET calculation disclose non-carcinogenic and relatively harmless phenomena for oral administration of all drugs.Keywords
This publication has 25 references indexed in Scilit:
- P-glycoprotein Inhibition for Optimal Drug DeliveryDrug Target Insights, 2013
- admetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET PropertiesJournal of Chemical Information and Modeling, 2012
- Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypesNature Reviews Drug Discovery, 2011
- ChemSpider: An Online Chemical Information ResourceJournal of Chemical Education, 2010
- A Medicinal Chemist’s Guide to Molecular InteractionsJournal of Medicinal Chemistry, 2010
- Identification of a GABAAReceptor Anesthetic Binding Site at Subunit Interfaces by Photolabeling with an Etomidate AnalogJournal of Neuroscience, 2006
- Quantifying Intermolecular Interactions: Guidelines for the Molecular Recognition ToolboxAngewandte Chemie, 2004
- Sudden Death and BenzodiazepinesAmerican Journal of Forensic Medicine & Pathology, 1996
- Density-functional exchange-energy approximation with correct asymptotic behaviorPhysical Review A, 1988
- Development of the Colle-Salvetti correlation-energy formula into a functional of the electron densityPhysical Review B, 1988