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

Authors

  • I. M. Podolsky National University of Pharmacy
  • S. Yu. Shtrygol' National University of Pharmacy
  • V. V. Tsyvunin National University of Pharmacy

DOI:

https://doi.org/10.11603/2312-0967.2018.1.8616

Keywords:

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.

Author Biographies

I. M. Podolsky, National University of Pharmacy

Ph.D in Pharmacy, associate professor of the Medicinal Chemistry Department of National University of Pharmacy

S. Yu. Shtrygol', National University of Pharmacy

D.Sc. in Medicine, Professor, Head of the Pharmacology Department of National University of Pharmacy

V. V. Tsyvunin, National University of Pharmacy

Ph.D in Pharmacy, assistant of the Pharmacology Department of National University of Pharmacy

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Published

2018-03-24

How to Cite

Podolsky, I. M., Shtrygol’, S. Y., & Tsyvunin, V. V. (2018). 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. Pharmaceutical Review Farmacevtičnij časopis, (1), 115–122. https://doi.org/10.11603/2312-0967.2018.1.8616

Issue

No. 1 (2018)

Section

Pharmacological researches of biologically active substances

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