IN SILICO RESEARCH OF THE POSSIBLE PATHWAYS OF ATRISTAMINE METABOLISM IN THE HUMAN BODY

  • I. M. Podolsky NATIONAL UNIVERSITY OF PHARMACY, KHARKIV
  • S. Yu. Shtrygol NATIONAL UNIVERSITY OF PHARMACY, KHARKIV
Keywords: atristamine, 2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one, metabolism, in silico research, Xenosite, Way2Drug

Abstract

Introduction. The object of the present study is atristamine (2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one), which is being studied as a promising antidepressant with cerebroprotective, nootropic, analgesic, antihypoxic and actoprotective properties. A prerequisite for its further introduction as a candidate for drugs is the study of the pharmacokinetic characteristics of the molecule. This is impossible without a holistic understanding of the biotransformation processes that the molecule undergoes in the human body.

The aim of the study – in silico study of the possible metaboliс pathways of the promising antidepressant atristamine using freely available online resources.

Research Methods. For the purpose of in silico research of possible directions of biotransformation of atristamine in the human body, the following online web services were used: Xenosite P450 Metabolism 1.0; Xenosite UGT 2.0; Way2Drug SOMP and Way2Drug RA. Taking into account that the structural feature of quinolin-4(1H)-ones is the possibility of prototropic tautomerism in the heterocycle, computations were performed for both theoretically possible tautomeric forms of the atristamine molecule – 2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one and 4-hydroxy-2-methyl-3-(phenylaminomethyl)-quinoline.

Results and Discussion. Due to the presence of a secondary amino group in the molecule of 2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one and 4-hydroxy group in the structure of another tautomer (4-hydroxy-2-methyl-3-(phenylaminomethyl)-quinoline) glucuronidation is highly probable with the formation of N- and O-glu­curonides, respectively. For 2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one as a more stable form, it was shown that aromatic hydroxylation, aliphatic hydroxylation, oxidative deamination, N-hydroxylation and epoxidation can be the main metabolic pathways. The direction of aliphatic hydroxylation deserves the most attention, since, unlike all other pathways, the formation of metabolites with new pharmacological properties (kynurenic acid derivatives) was predicted as a result of this.

Conclusions. The results of in silico research of possible pathways of atristamine metabolism in the human body support the fact that this molecule with high probability can be intensively metabolized via cytochrome P450 enzyme systems. This must be taken into account when planning in vivo experiments in the future.

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Published
2019-11-07
How to Cite
Podolsky, I. M., & Shtrygol, S. Y. (2019). IN SILICO RESEARCH OF THE POSSIBLE PATHWAYS OF ATRISTAMINE METABOLISM IN THE HUMAN BODY. Medical and Clinical Chemistry, (3), 44-52. https://doi.org/10.11603/mcch.2410-681X.2019.v.i3.10558
Section
ORIGINAL INVESTIGATIONS