Oleksii Antypenko

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.

Antimicrobial resistance is a never‐ending challenge, which should be considered seriously, especially when using unprescribed “over‐the‐counter” drugs. The synthesis and investigation of novel biologically active substances is among the directions to overcome this problem. Hence, 18 novel 5,6‐dihydrotetrazolo[1,5‐ c ]quinazolines were synthesized, their identity, purity, and structure were elucidated by elemental analysis, IR, LC‐MS, 1 Н, and 13 C NMR spectra. According to the computational estimation, 15 substances were found to be of toxicity Class V, two of Class IV, and only one of Class II. The in vitro serial dilution method of antimicrobial screening against Escherichia coli, Staphylococcus aureus, Klebsiella aerogenes, Pseudomonas aeruginosa , and Candida albicans determined b3 , c1 , c6 , and c10 as the “lead‐compounds” for further modifications to increase the level of activity. Substance b3 demonstrated antibacterial activity that can be related to the calculated high affinity toward all studied proteins: 50S ribosomal protein L19 (PDB ID: 6WQN), sterol 14‐alpha demethylase (PDB ID: 5TZ1), and ras‐related protein Rab‐9A (PDB ID: 1WMS). The structure–activity and structure–target affinity relationships are discussed. The targets for further investigations and the anatomical therapeutic chemical codes of drug similarity are predicted.