Cargando…
Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach
A comparative Hansch 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-phenylquin...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034086/ http://dx.doi.org/10.3390/ph3103167 |
_version_ | 1782317928555741184 |
---|---|
author | Sharma, Manish Gupta, Vipin B. |
author_facet | Sharma, Manish Gupta, Vipin B. |
author_sort | Sharma, Manish |
collection | PubMed |
description | A comparative Hansch 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. |
format | Online Article Text |
id | pubmed-4034086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-40340862014-05-27 Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach Sharma, Manish Gupta, Vipin B. Pharmaceuticals (Basel) Article A comparative Hansch 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. MDPI 2010-10-11 /pmc/articles/PMC4034086/ http://dx.doi.org/10.3390/ph3103167 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Sharma, Manish Gupta, Vipin B. Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title | Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title_full | Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title_fullStr | Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title_full_unstemmed | Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title_short | Dual Allosteric Effect in Glycine/NMDA Receptor Antagonism: A Comparative QSAR Approach |
title_sort | dual allosteric effect in glycine/nmda receptor antagonism: a comparative qsar approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034086/ http://dx.doi.org/10.3390/ph3103167 |
work_keys_str_mv | AT sharmamanish dualallostericeffectinglycinenmdareceptorantagonismacomparativeqsarapproach AT guptavipinb dualallostericeffectinglycinenmdareceptorantagonismacomparativeqsarapproach |