Molecular docking analysis of α2-containing GABAA receptors with benzimidazoles derivatives.

Abdellatif Bouayyadi,Aissam El Aliani,Najia El Abbadi,Abdelhalim Mesfioui,Mohammed El Mzibri,Yassine Kasmi,Ahmed Moussaif,El Mokhtar Essassi

doi:10.6026/97320630016611

Abdellatif Bouayyadi, Aissam El Aliani + Show 6 more

Open Access

https://doi.org/10.6026/97320630016611

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Abstract

It is of interest to study the binding capacity of "3-[2-(2-Amino-1H-benzo[d]imidazol-1-yl)ethyl]-1,3-oxazolidin-2-one" (OXB2) with the active site of gamma-aminobutyric acid (GABA) located in the GABA type A receptor (GABAAR) in comparison with different GABAA subtypes. Optimal binding features were observed with the α2β2γ2 isoform (-8 kcal/mol). This is similar (-7.3 and -7.2 kcal/mol, respectively) for subtypes (α3β2γ2 and α1β2γ2). This implies that OXB2 binds preferentially to subtypes associated with anxiety (α2- and/or α3-containing receptors) linked molecules than with the subtype associated with sedation (α1-containing receptors). It is further noted that molecular dynamics simulation data of the complex (OXB2-GABAAR) shows adequate structural stability in aqueous environment. Moreover, relevant ADMET data is found adequate for further consideration.

Highlights

There is increasing interest to molecules containing heterocyclic ring, constituting the basic skeleton for a wide variety of compounds with industrial and pharmacological activities [1,2]
These classes of psychoactive drugs are widely used for treatment of psychotropic diseases, especially Generalized Anxiety Disorder (GAD) [4,5]
GABAA receptors are pentameric proteins composed of different subunits (α1-6, β1-3, γ1-3, δ, ε, π and θ), α subunit being the most important one determining the pharmacology of the Benzodiazepines binding site [11]

Summary

Research Article

Molecular docking analysis of α2-containing GABAA receptors with benzimidazoles derivatives. Declaration on Publication Ethics: The authors state that they adhere with COPE guidelines on publishing ethics as described elsewhere at https://publicationethics.org/. The authors undertake that they are not associated with any other third party (governmental or non-governmental agencies) linking with any form of unethical issues connecting to this publication. The authors declare that they are not withholding any information that is misleading to the publisher in regard to this article. The authors are responsible for the content of this article.

Background

Results & Discussion

Plasma Protein Binding Pgp inhibition MDCK

Conclusion