The present article is devoted to searching for biologically active agents among novel thio-containing pteridines. Synthetic protocols based on the condensation of 5,6diamino-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones with dicarbonyl compounds were elaborated and used for the synthesis of target products. The directions for further modification of the obtained thio-containing pteridines were substantiated and realized. The spectral properties of the obtained compounds were studied and described. The results of the in silico study revealed that the predicted affinity of the obtained compounds to the dihydrofolate reductase (DHFR) active site is comparable with the affinity of methotrexate, despite the differences in the nature of the ligand-enzyme interactions. The in vitro study of DHFR-inhibiting activity revealed that the most active compounds 3.9 and 4.2 have lg IC 50 values of −5.889 and −5.233, respectively, significantly inferior to methotrexate (lg IC 50 = −7.605).Additionally, the synthesized compounds were studied for their antiradical activity as a possible mechanism of pharmacological effects. Among the obtained pteridines, compounds 5.1 (lg EC 50 = −4.82) and 5.3 (lg EC 50 = −4.92) have antiradical activity higher than the reference compound ascorbic acid (lg EC 50 = −4.81). The conducted structure-activity relationship analysis provided valuable data for the further search for biologically active agents among thio-containing pteridines and related compounds.
Liver damage is a common problem around the world, and pharmacocorrection of such disease is carried out by administration of various drugs. Natural and synthetic thio-containing compounds are important in this respect. Most of these, however, have side effects and do not always meet the criteria of evidence-based medicine. Therefore, the search for new drugs with hepatoprotective properties, characterized by high efficiency and low toxicity, is an urgent problem of current pharmacology and biochemistry. The purpose of this study was to assess the acute toxicity of new potentially bioactive S-substituted pteridinones, to select the least toxic substance, to improve the pharmaco-technological characteristics, and to study the hepatoprotective properties in an experimental model of tetrachloromethane hepatitis in rats. Herein, comparison of the hepatoprotective properties of compound 4.1 and the reference drug "Thiotriazoline" is based on biochemical studies. The research results showed that sub-stance 4.1 had a positive effect on biochemical processes by increasing the compensatory mechanisms of antioxidant systems, while reducing the infiltrative, destructive and inflamma-tory process in the liver, evoking decreases in the cytolytic process, restoring the structure of the components of the membrane of hepatocytes, stabilizing and enhancing the functional activity of the liver, restoring the liver’s protein-synthesizing function and increasing the abil-ity to restore metabolic disorders in the liver. As a result of the biochemical study of the hepa-toprotective effect of compound 4.1, it was found that the studied substance is a non-toxic compound with antioxidant properties.
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