II. Synthesis and Antioxidant Activity of Hydrazinecarbothioamides Based on 6-Methyluracil and Acylhydrazides

Abstract

Objective: The synthesis of uracil-containing hydrazinecarbothioamides opens up new possibilities for studying their antioxidant properties. In the course of this work, the indicated compounds with high yields were successfully obtained. Their antioxidant potential has been studied in vitro using conventional techniques such as ABTS, FRAP, DPPH, and nitric oxide inhibition tests. Methods: The synthesis of hydrazinecarbothioamides was carried out by the method described earlier, by boiling 5-isothiocyanato-6-methyluracil and acylhydrazides in a 1,4-dioxane medium with quantitative yields. When studying the antioxidant activity in vitro of the obtained compounds, ascorbic acid and trolox were used as comparison drugs. Results and Discussion: The reaction of 5-isothiocyanato-6-methyluracil and acylhydrazides synthesized a series of hydrazinecarbothioamides with high yields and investigated their biological activity. During in vitro tests for antioxidant properties, it was found that compound (VII), which contains in its structure, in addition to 6-methyluracil and thiourea, an aromatic fragment, has the best activity against the reduction of Fe³⁺ and the radical cation ABTS. It was shown that compound (XI), containing an isonicotinoyl fragment in its structure, was more active in reducing the stable DPPH radical and inhibiting nitric oxide. Conclusions: As a result, two of the most active compounds were identified: 2-benzoyl-N-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)hydrazinecarbothioamide (showed reducing activity against the radical cation ABTS and Fe³⁺ in EC₅₀ values of 276.31 ± 11.52 and 10.14 ± 0.45 µg/mL, respectively) and 2-isonicotinoyl-N-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)hydrazinecarbothioamide (restored the stable radical DPPH in the EC₅₀ value of 124.28 ± 4.32 µg/ml, and also reduced the level of nitrite by 55.9% (p < 0.05) compared with the control).