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 (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.