Objective: Synthesis of hybrid molecules combining various pharmacophore fragments. In this work, the synthesis of hydrazinecarbothioamides with a fragment of 6-methyluracil was carried out to develop drugs, and their antioxidant properties were studied in vitro on models of ABTS, FRAP, DPPH, and nitric oxide inhibition. Methods: The synthesis of hydrazinecarbothioamides with a fragment of 6-methyluracil was carried out using 5-isothiocyanato-6-methyluracil as a substrate. The reaction was carried out by boiling 5-isothiocyanato-6-methyluracil in 1,4-dioxane with the corresponding hydrazines. To study the antioxidant activity, the obtained compounds were dissolved in DMSO and EtOH at concentrations of: 1, 10, 50, 100, and 200 µg/mL. Ascorbic acid and trolox were used as comparison drugs. Each concentration of the compound samples was studied in three parallel analyses. The results are presented as the mean (M) and the mean error of the mean (± SEM). The AOA of the compounds was expressed as their effective concentration (EC50, µg/mL), at which a 50% reduction of DPPH, ABTS+ radicals, or a reduction of Fe(III) to Fe(II) from their total content in the reaction mixture occurs. Results and Discussion: With yields of 85–92%, the synthesis of hydrazinecarbothioamides with a fragment of 6-methyluracil was carried out using 5-isothiocyanato-6-methyluracil as a substrate. The structure of the synthesized compounds was established on the basis of NMR, mass spectroscopy, and elemental analysis data. In order to identify the antioxidant activity, the obtained compounds were studied in vitro on models of ABTS, FRAP, DPPH and nitric oxide inhibition. Among the synthesized hydrazinecarbothioamides, compounds exhibiting antioxidant activity higher than the comparison drugs, ascorbic acid and trolox, were identified. Conclusions: Hydrazinecarbothioamides with a 6-methyluracil fragment with high yields were synthesized and their biological activity was investigated. The study of the antioxidant activity of the obtained compounds using Fe3+ reduction, ABTS cation, stable radical DPPH, and nitric oxide inhibition assays in vitro has revealed several compounds with high antioxidant activity, among which the leader 2-(2,4-dinitrophenyl)-N-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)hydrazinecarbothioamide, containing a dinitrophenyl substituent in its structure, has been selected for in-depth study.
Chernikova et al. (Fri,) studied this question.