BACK TO CONTENTS   |    PDF   |    PREVIOUS   |    NEXT

Title

In-silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives

 

Authors

Faizul Azam1*, Ismaiel Mohamed Abugrain1, 2, Mohamed Hussin Sanalla1, Radwan Fatahalla Elnaas1 & Ibrahim Abdassalam Ibn Rajab1

 

Affiliation

1Faculty of Pharmacy, Misurata University, PO Box 2873, Misurata, Libya; 2School of Pharmacy, University of Bradford, Bradford, West Yorkshire, United Kingdom

 

Email

faizulazam@gmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received September 27, 2013; Accepted October 01, 2013; Published October 16, 2013

 

Abstract

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 (r2 = 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 π-π 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.

 

Keywords

Docking; AMPA receptor antagonist; Neurological disorders; Quinoxaline derivatives

 

Citation

Azam et al.   Bioinformation 9(17): 864-869 (2013)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.