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in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives

Glutamate receptors have been implicated in various neurological disorders and their antagonism offers a suitable approach for the treatment of such disorders. The field of drug design and discovery aims to find best medicines to prevent, treat and cure diseases quickly and efficiently. In this rega...

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Detalles Bibliográficos
Autores principales: Azam, Faizul, Abugrain, Ismaiel Mohamed, Sanalla, Mohamed Hussin, Elnaas, Radwan Fatahalla, Rajab, Ibrahim Abdassalam Ibn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819572/
https://www.ncbi.nlm.nih.gov/pubmed/24250113
http://dx.doi.org/10.6026/97320630009864
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author Azam, Faizul
Abugrain, Ismaiel Mohamed
Sanalla, Mohamed Hussin
Elnaas, Radwan Fatahalla
Rajab, Ibrahim Abdassalam Ibn
author_facet Azam, Faizul
Abugrain, Ismaiel Mohamed
Sanalla, Mohamed Hussin
Elnaas, Radwan Fatahalla
Rajab, Ibrahim Abdassalam Ibn
author_sort Azam, Faizul
collection PubMed
description Glutamate receptors have been implicated in various neurological disorders and their antagonism offers a suitable approach for the treatment of such disorders. The field of drug design and discovery aims to find best medicines to prevent, treat and cure diseases quickly and efficiently. In this regard, computational tools have helped medicinal chemists modify and optimize molecules to potent drug candidates with better pharmacokinetic profiles, and guiding biologists and pharmacologists to explore new disease genes as well as novel drug targets. In the present study, to understand the structural requirements for AMPA receptor antagonism, molecular docking study was performed on 41 structurally diverse antagonists based on quinoxaline nucleus. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results obtained signify that the molecular docking approach is reliable and produces a good correlation coefficient (r(2) = 0.6) between experimental and docking predicted AMPA receptor antagonistic activity. The aromatic moiety of quinoxaline core has been proved to be vital for hydrophobic contacts exhibiting - interactions in docked conformations. However, polar moieties such as carboxylic group and 1,2,4-triazole moieties were noted to be sites for hydrophilic interactions in terms of hydrogen bonding with the receptor. These analyses can be exploited to design and develop novel AMPA receptor antagonists for the treatment of different neurological disorders.
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spelling pubmed-38195722013-11-18 in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives Azam, Faizul Abugrain, Ismaiel Mohamed Sanalla, Mohamed Hussin Elnaas, Radwan Fatahalla Rajab, Ibrahim Abdassalam Ibn Bioinformation Hypothesis Glutamate receptors have been implicated in various neurological disorders and their antagonism offers a suitable approach for the treatment of such disorders. The field of drug design and discovery aims to find best medicines to prevent, treat and cure diseases quickly and efficiently. In this regard, computational tools have helped medicinal chemists modify and optimize molecules to potent drug candidates with better pharmacokinetic profiles, and guiding biologists and pharmacologists to explore new disease genes as well as novel drug targets. In the present study, to understand the structural requirements for AMPA receptor antagonism, molecular docking study was performed on 41 structurally diverse antagonists based on quinoxaline nucleus. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results obtained signify that the molecular docking approach is reliable and produces a good correlation coefficient (r(2) = 0.6) between experimental and docking predicted AMPA receptor antagonistic activity. The aromatic moiety of quinoxaline core has been proved to be vital for hydrophobic contacts exhibiting - interactions in docked conformations. However, polar moieties such as carboxylic group and 1,2,4-triazole moieties were noted to be sites for hydrophilic interactions in terms of hydrogen bonding with the receptor. These analyses can be exploited to design and develop novel AMPA receptor antagonists for the treatment of different neurological disorders. Biomedical Informatics 2013-10-16 /pmc/articles/PMC3819572/ /pubmed/24250113 http://dx.doi.org/10.6026/97320630009864 Text en © 2013 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
spellingShingle Hypothesis
Azam, Faizul
Abugrain, Ismaiel Mohamed
Sanalla, Mohamed Hussin
Elnaas, Radwan Fatahalla
Rajab, Ibrahim Abdassalam Ibn
in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title_full in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title_fullStr in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title_full_unstemmed in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title_short in Silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives
title_sort in silico investigation of the structural requirements for the ampa receptor antagonism by quinoxaline derivatives
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819572/
https://www.ncbi.nlm.nih.gov/pubmed/24250113
http://dx.doi.org/10.6026/97320630009864
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