The thesis is devoted to the search for new bioactive compounds in the series of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols derivatives with potential antimicrobial, antifungal, antihypoxic and antioxidant activity, establishing some "structure-activity relationship" patterns, and further recommendations due to the compounds that can be candidates for the creation of potential drugs’ active substances. Within the framework of the study, two starting substances 4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazol-3-thiol and 4-ethyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol were synthesized by cyclization of the corresponding thiosemicarbazides in an alkaline environment. A plausible model of mass spectrometric fragmentation of 4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol under GC-MS analysis conditions was proposed. The next step was the synthesis of 4-(5-(((4-alkyl-5-(alkylthio)-4H-1,2,4-triazole-3-yl)methyl)thio)-1H-1,2,4-triazole-3-yl)pyridines. In further studies, the reaction of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols with 2-chloroacetate acid was investigated by boiling in methanol in an alkaline medium, resulting in the formation of 2-((4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)acetic acids. The next stage of the work was isopropyl esters’ obtaining of the corresponding acids by 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols alkylation with isopropyl ester of 2-chloroacetic acid in the presence of potassium hydroxide. Next, the 2-((4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-1-(aryl)etan-1-ones and 2-((4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-1-ethan-1-ones were synthesized by the alkylation method of the starting thiols with the corresponding 2-bromo-1-arylethanones and 1-bromopropan-2-one in the medium of propan-2-ols in the presence of an equivalent amount of potassium hydroxide. For the synthesis of potential candidate compounds containing an asymmetric carbon atom, 2-((4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-1-(aryl)ethan-1-ones were selected, which were reduced to the corresponding alcohols by adding a double amount of sodium borohydride. Additionally, 2-((4-ethyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ols were obtained by alkylation of the starting thiols with 2-chloroethanol in the presence of an equivalent amount of potassium hydroxide. Рolarimetric studies were conducted on the synthesized 1-((4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-2-arylethan-1-ols by measuring the rotation’s angle of the polarization surface of their solutions. N-substituted acetamides of 1,2,4-triazoles can exhibit antibacterial and antioxidant activity, so their synthesis is of great practical and theoretical importance. Spectral and physicochemical parameters of new derivatives 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols was established using modern complex methods of analysis, including 1H-NMR spectroscopy, elemental analysis, gas mass spectrometry. Using web services, the toxicity of the synthesized 1,2,4-triazole compounds was predicted, as a result of which the safest compound was 2-((4-ethyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl-4H-1,2,4-triazole-3-yl)thio)acetic acid. Subsequently, the acute acid toxicity and its organic and inorganic salts was studied on the hydrobiont Zebrafish (Danio rerio). The results of the biological screening for antimicrobial and antifungal activity of all synthesized derivatives of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols with alkyl, acyl-alkyl, isopropyl, acyl-aryl, and amide residues indicate moderate inhibition of the growth of the tested strains. According to the results in vivo studies, the compound 1-((4-ethyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)propan-2-one has showed an antihypoxic effect, exceeding the activity of the reference drug in 2.4%. Molecular modeling study for the system with the best docking score of NO-synthase with 1-(4-fluorophenyl)-2-((4-ethyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)ethanone has demonstrated the formation of a stable complex throughout the simulation, which indicates the prospect of further research of antioxidant activity in vivo.
