Evaluation of immunotoxic properties of pyrimidine derivatives

Abstract

Introduction. Currently, the problem of developing safe anti-infective drugs with antibacterial action against a wide range of pathogens is acute. In this regard, one of the main tasks of the preclinical stage of the development of potential drugs is to assess their possible toxic effects on the body as a whole and various systems, including the immune system. Pyrimidine derivatives are of particular interest as new active substances. Being an integral part of nucleic acids, pyrimidine bases provide a wide pharmacological activity, as well as a high profile of drug safety of drugs synthesized on their basis. Pyrimidine compounds have been found to have psycho- and neurotropic, sedative, immunotropic, regenerative, antitumor, antiviral, antimicrobial and other types of action.

The aim of the study was to evaluate the immunotoxic properties of the pyrimidine derivatives.

Material and methods. The study was carried out on 30 male mice of the NEA line 7–8 weeks of age with a body weight of 20–22 g. The animals were divided into groups: «control» – mice receiving intraperitoneal equivalent volume of water for injection; experimental animals receiving intraperitoneal for three days pyrimidine compounds 3-[2-(Naphthyl)-2-oxoethyl]-6-bromoquinazoline-4(3H)-on (VMA–13–06) at a dose of 39 mg/kg and 3-(2-Ter.- butyl-2-oxoethyl)quinazolin-4(3H)-on (VMA–13–11) at a dose of 24 mg/kg. The dose of the pyrimidine derivative was 1/10 of the molecular weight of the compound. Immunotoxic properties were evaluated according to the «Guidelines for conducting preclinical studies of medicines» (Mironov A.N., 2012) according to the following indicators: mass and cellularity of immune-competent organs; delayed-type hypersensitivity reaction (DTH); direct hemagglutination reaction (DAT); phagocytic activity of neutrophils (number of active neutrophils, phagocytic index and phagocytic number).

Results. It was found that the pyrimidine derivative 3-[2-(Naphthyl)-2-oxoethyl]-6-bromoquinazoline-4(3H)-on had an immunosuppressive effect on the cellular and humoral links of immunity, which manifested itself in a decrease in the mass and cellularity of the spleen, the DTH index and antibody titer in DAT, as well as a decrease in the phagocytic function of neutrophils, whereas the compound 3-(2-Tert.-butyl-2-oxoethyl)quinazoline-4(3H)-on did not have an immunosuppressive effect on the studied parameters.

Conclusion. Thus, the conducted studies indicate the absence of a new pyrimidine derivative 3-(2-Tert.-butyl-2-oxoethyl)quinazoline-4(3H)-on has immunotoxic properties, which makes it possible to further study in detail the pharmacological activity of this compound.

Keywords:pyrimidine derivatives; immunotropism; immunotoxicity; immunosuppression; cellular immunity; humoral immunity

For citation: Yasenyavskaya A.L., Tsibizova A.A., Ozerov A.A., Tyurenkov I.N., Bashkina O.A., Samotrueva M.A. Evaluation of immunotoxic properties of pyrimidine derivatives. Immunologiya. 2022; 43 (3): 312–9. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-312-319 (in Russian)

Funding. The work was carried out within the framework of the state task of the Ministry of Health of the Russian Federation regarding research on the topic «Search and development of promising compounds with antibacterial activity among pyrimidine derivatives for the creation of medicines» 48.2-2021

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Data collection, text writing, analysis of the results, preparation of a draft manuscript – Yasenyavskaya A.L.; data collection, evaluation, substantiation and statistical processing of the obtained data, preparation of a draft manuscript – Tsibizova A.A.; research planning, manuscript editing, evaluation of the results – Ozerov A.A.; research planning, manuscript editing, evaluation of the results – Tyurenkov I.N.; research planning, manuscript editing, evaluation of the results; final approval of the manuscript for publication – Bashkina O.A.; development of the concept and design of the study, research planning, verification of critical intellectual content, final approval of the manuscript for publication – Samotrueva M.A.

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EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Вскрытие
Medicine today

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