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Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics

Rhinitis is an allergic disease that causes troubles and restlessness for patients. In this research work we will focus on finding promising organic molecules with potential ability to target histamine receptor with no sedative side effect. Phalazines and their isosteres, pyrimidines and pyridines h...

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Autores principales: Xiaopeng Sun, Belal, Amany, Elanany, Mohamed A., Alsantali, Reem I., Alrooqi, Munira M., Mohamed, Abdalla R., Hasabelnaby, Sherifa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pleiades Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134989/
https://www.ncbi.nlm.nih.gov/pubmed/35637779
http://dx.doi.org/10.1134/S1068162022330019
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author Xiaopeng Sun
Belal, Amany
Elanany, Mohamed A.
Alsantali, Reem I.
Alrooqi, Munira M.
Mohamed, Abdalla R.
Hasabelnaby, Sherifa
author_facet Xiaopeng Sun
Belal, Amany
Elanany, Mohamed A.
Alsantali, Reem I.
Alrooqi, Munira M.
Mohamed, Abdalla R.
Hasabelnaby, Sherifa
author_sort Xiaopeng Sun
collection PubMed
description Rhinitis is an allergic disease that causes troubles and restlessness for patients. In this research work we will focus on finding promising organic molecules with potential ability to target histamine receptor with no sedative side effect. Phalazines and their isosteres, pyrimidines and pyridines have been reported to target H1 receptors, for this reason we have searched for library of these basic scaffolds, this library which has 184 organic molecules will be subjected for further explorations through computer aided drug design techniques. Swiss ADMET will be used to gather these compounds in clusters. Cluster with low potential to penetrate BBB is selected for virtual screening through pharmacophore model. Then molecular docking that revealed the stability of the complex formed between the investigated molecules and H1 receptor. ADMET profile showed three compounds (XVIII), (XX), and (XXI) with no toxicity on liver and no effect on CYP2D6, these three compounds were subjected to molecular dynamic simulations and compound (XVIII) showed the most stable complex with the target protein (H1). Finally, we can say this work helped us to find new compounds with promising potential to target H1 without ability to penetrate BBB, so they can be used as useful candidates in treatment of rhinitis and deserve to be subjected for preclinical and clinical investigations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1134/S1068162022330019.
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spelling pubmed-91349892022-05-26 Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics Xiaopeng Sun Belal, Amany Elanany, Mohamed A. Alsantali, Reem I. Alrooqi, Munira M. Mohamed, Abdalla R. Hasabelnaby, Sherifa Russ J Bioorg Chem Article Rhinitis is an allergic disease that causes troubles and restlessness for patients. In this research work we will focus on finding promising organic molecules with potential ability to target histamine receptor with no sedative side effect. Phalazines and their isosteres, pyrimidines and pyridines have been reported to target H1 receptors, for this reason we have searched for library of these basic scaffolds, this library which has 184 organic molecules will be subjected for further explorations through computer aided drug design techniques. Swiss ADMET will be used to gather these compounds in clusters. Cluster with low potential to penetrate BBB is selected for virtual screening through pharmacophore model. Then molecular docking that revealed the stability of the complex formed between the investigated molecules and H1 receptor. ADMET profile showed three compounds (XVIII), (XX), and (XXI) with no toxicity on liver and no effect on CYP2D6, these three compounds were subjected to molecular dynamic simulations and compound (XVIII) showed the most stable complex with the target protein (H1). Finally, we can say this work helped us to find new compounds with promising potential to target H1 without ability to penetrate BBB, so they can be used as useful candidates in treatment of rhinitis and deserve to be subjected for preclinical and clinical investigations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1134/S1068162022330019. Pleiades Publishing 2022-05-26 2022 /pmc/articles/PMC9134989/ /pubmed/35637779 http://dx.doi.org/10.1134/S1068162022330019 Text en © Pleiades Publishing, Ltd. 2022, ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2022, Vol. 48, No. 2, pp. 438–456. © Pleiades Publishing, Ltd., 2022. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Xiaopeng Sun
Belal, Amany
Elanany, Mohamed A.
Alsantali, Reem I.
Alrooqi, Munira M.
Mohamed, Abdalla R.
Hasabelnaby, Sherifa
Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title_full Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title_fullStr Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title_full_unstemmed Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title_short Identification of Some Promising Heterocycles Useful in Treatment of Allergic Rhinitis: Virtual Screening, Pharmacophore Mapping, Molecular Docking, and Molecular Dynamics
title_sort identification of some promising heterocycles useful in treatment of allergic rhinitis: virtual screening, pharmacophore mapping, molecular docking, and molecular dynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134989/
https://www.ncbi.nlm.nih.gov/pubmed/35637779
http://dx.doi.org/10.1134/S1068162022330019
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