Synthesis and antimicrobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol

Abstract

The aim of the work. 1,2,4-triazole derivatives possess a wide range of pharmacological activity, so they are used for the development of drugs and active pharmaceutical ingredients. Due to the reactivity of 1,2,4-triazoles there are many options for their further structural modification on different reaction centers. Therefore, the aim of the work was to obtain new S-substituted derivatives of 1,2,4-triazole-3-thiols, study physicochemical parameters of the substances synthesized, evaluate the antimicrobial activity of new S-derivatives of the 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol series, and study some regularities of the “structure – biological activity” relationship for the synthesized compounds as well.
 Materials and methods. The subject of the study was new S-substituted 1,2,4-triazoles containing 2-oxopropan-1-yl and 2-aryl-2-oxoethan-1-yl substituents. The antimicrobial activity was studied by double serial dilutions on test cultures of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 885-653).
 The results of the biological screening showed that at a concentration of 125 g/mL, all synthesized substances showed activity (MIC – in the range of 31.25 - 62.5 μg/mL, MBCK - in the range of 62.5–125 μg/mL) against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans. Variation of substituents on the sulfur atom did not lead to a significant change in antimicrobial and antifungal activities among derivatives of 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl) thio)methyl)-4H-1,2,4-triazole-3-thiols.
 Conclusions. Biological screening data indicate the prospects for the search for new antimicrobial substances among the abovementioned derivatives of 1,2,4-triazoles. The most active compounds were 1-((4-ethyl-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)propan-2-one and 1-(4-methoxyphenyl)-2-(4-ethyl-5-(((3-(pyridin-4-yl)-1H)-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)ethanone, which showed the most pronounced antimicrobial activity against the Pseudomonas aeruginosa strain (MIC – 31.25 μg/mL, MBcK - 62.5 μg/mL)

Evaluation Of Antioxidant Activity Of 1, 2, 4-Triazole Derivatives With Morpholine Moiety

“…Analyzing the array of scientific data, a special attention should be noted to the derivatives of 1,2,4-triazole [6,7]. This nitrogen-containing, heterocyclic system is increasingly attracting the attention of scientists, which based at their level of a wide and pronounced range of biological and pharmacological [8][9][10][11][12][13][14] actions and low toxicity parameters [7,11,15]. 1,2,4-Triazole derivatives are quite convenient agents in terms of "fine" organic synthesis [16][17][18] and in terms of relative safety of reagents [19,20].…”

“…1,2,4-Triazole derivatives are quite convenient agents in terms of "fine" organic synthesis [16][17][18] and in terms of relative safety of reagents [19,20]. Therefore, based on the results of synthetic scientific schools [4,[6][7][8][9][10][11] and our own work [12][13][14][15]18], we considered it appropriate to study the antioxidant activity (AOA) of 4-R-3-(morpholinomethyl)-4H-1,2,4-triazole-5-thioles and their alkyl derivatives in vitro using the method of non-enzymatic initiation of lipid peroxidation.…”