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Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach
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
Abstract: 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
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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.
Sharma M, Gupta VB. Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach. Pharmaceuticals. 2010; 3(10):3167-3185.
Sharma, Manish; Gupta, Vipin B. 2010. "Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach." Pharmaceuticals 3, no. 10: 3167-3185.