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Pharmaceuticals 2010, 3(10), 3167-3185; doi:10.3390/ph3103167

Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach

*  and
Centre for QSAR and Molecular Modeling, Department of Medicinal and Pharmaceutical Chemistry, TIFAC-CORE, Innovation Square, B. R. Nahata College of Pharmacy (Scientific and Industrial Research Organization), Mandsaur, 458001, MP, India
* Author to whom correspondence should be addressed.
Received: 13 August 2010 / Accepted: 25 September 2010 / Published: 11 October 2010
(This article belongs to the Special Issue Allosteric Modulation)
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A comparative Hantzsch type QSAR study was conducted using multiple regression analysis on various sets of quinoxalines, quinoxalin-4-ones, quinazoline-2-carboxylates, 4-hydroxyquinolin-2(1H)-ones, 2-carboxytetrahydroquinolines, phenyl-hydroxy-quinolones, nitroquinolones and 4-substituted-3-phenylquinolin-2(1H)-ones as selective glycine/NMDA site antagonists. Ten statistically validated equations were developed, which indicated the importance of CMR, Verloop’s sterimol L1 and ClogP parameters in contributing towards biological activity. Interestingly, normal and inverse parabolic relationships were found with CMR in different series, indicating a dual allosteric binding mode in glycine/NMDA antagonism. Equations reveal an optimum CMR of 10 ± 10% is required for good potency of antagonists. Other equations indicate the presence of anionic functionality at 4-position of quinoline/quinolone ring system is not absolutely required for effective binding. The observations are laterally validated and in accordance with previous studies.
Keywords: allosterism; comparative QSAR; glycine/NMDA; CMR; quinoxalines allosterism; comparative QSAR; glycine/NMDA; CMR; quinoxalines
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sharma, M.; Gupta, V.B. Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach. Pharmaceuticals 2010, 3, 3167-3185.

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