Open AccessInvestigation of NMDA Receptor Channel Blockers in a Series of Methylene Blue Conjugates Using QSAR and Molecular Modeling
Author(s) -
Grigor'ev Va,
K.A. Shcherbakov,
D. E. Polianczyk,
Alexander N. Razdolsky,
A. V. Veselovsky,
V. V. Grigoriev,
A. V. Yarkov,
Oleg A. Raevsky
Publication year - 2019
Publication title -
biomedical chemistry: research and methods
Language(s) - English
Resource type - Journals
ISSN - 2618-7531
DOI - 10.18097/bmcrm00091
Subject(s) - quantitative structure–activity relationship , docking (animal) , chemistry , hydrogen bond , stereochemistry , methylene , molecular model , carbazole , nmda receptor , computational chemistry , molecule , receptor , organic chemistry , biochemistry , medicine , nursing
29 conjugates of methylene blue and four chemical structures, including derivatives of carbazole, tetrahydrocarbazole, substituted indoles and γ-carboline, combined with a 1-oxopropylene spacer have been studied as channel blockers of the NMDA receptor (binding site of MK-801) by using four QSAR methods (multiple linear regression, random forest, support vector machine, Gaussian process) and molecular docking. QSAR models have satisfactory characteristics. The analysis of regression models at the statistical level revealed an important role of the hydrogen bond in the complex formation. This was also confirmed by the study of modeled by docking complexes. It was found that the increase in the inhibitory activity of the part of compounds could be attributed to appearance of additional H bonds between the ligands and the receptor.