COMPARATIVE ANALYSIS OF IN VIVO SCREENING AND IN SILICO PREDICTION RESULTS OF PSYCHO- AND NEUROTROPIC PROPERTIES OF 3-(N-R,R'-AMINOMETHYL)-2-METHYL-1H-QUINOLIN-4-ONES
DOI:
https://doi.org/10.11603/2312-0967.2018.1.8616Keywords:
3-(N-R, R'-aminomethyl)-2-methyl-1H-quinoline-4-ones, neurotropic activity, atristamine, computer-aided prediction, PASS Online.Abstract
The aim of the work. To analyze and compare the results of screening in vivo studies and retrospective in silico prediction of the psycho- and neurotropic properties of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones.
Materials and Methods. Analysis of the results of previous screening in vivo studies of the psycho- and neurotropic properties of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones was based on the data published previously. Computer-aided prediction of the spectrum of the biological properties of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones was carried out retrospectively using the PASS Online system.
Results and Discussion. Systematization and analysis of the results of previous experimental pharmacological studies showed that the most of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones presented have pronounced nootropic properties, which for some derivatives are combined with high antidepressant activity, anti-anxiety effect, sedative or, conversely, stimulating properties. Analysis of the results for subgroups of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinolin-4-ones allowed us to reveal certain relationships between the chemical structure and the profile of the biological action.
The results of the PASS-prediction showed that the most probable biological effects of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones are the ability to act as inhibitors of ubiquinol-cytochrome c reductase, gluconate 2-dehydrogenase, plastoquinol-plastocyanin reductase, platelet-derived growth factor receptor kinase and 3-hydroxy-3-methylglutaryl-CoA synthase 2 expression enhancers. Parameters for effects that may even indirectly affect the functions of the CNS (calcium channel (voltage-sensitive) activator and 5-hydroxytryptamine release inhibitor) have significantly lower values.
Conclusions. It was justified, that using the computer-aided prediction of the pharmacological activity spectrum of 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinoline-4-ones applying the PASS program as the fundamental basis for further screening studies this class of compounds would have been lost as a promising in the search for new substances that can influence the functions of the central nervous system.
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