No abstract

A series of 1,2,4-benzothiadiazine-1,1-dioxides bearing a sulfonylthiourea moiety were synthesized, characterized, and screened for their antioxidant activity, using six antioxidant analytical assays comparatively to reference compounds, ascorbic acid and quercetin. The results indicated that several compounds demonstrated strong antioxidant activity in DPPH, ABTS, H2O2, and lipid peroxidation assays where some of them were either as active as or more active than reference compounds. However, all compounds were largely less active than references compounds in the reducing power assay. The results indicated that the thiourea moiety probably played a crucial role in the antioxidant activity of the target compounds, as a thiolate ion. The most favorable R1 groups were the hydrogen atom and methyl group, followed by phenyl and benzyl groups, whereas the most favorable R2 group was iPr, followed by the phenyl and methyl groups. The combination of benzothiadiazine ring with sulfonylthiourea moieties led to valuable new antioxidants, which could be used in the treatment or the prevention of certain diseases or in the field of cosmetics, which needs further investigations in the future.

A series of novel 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties were synthesized and pharmacologically evaluated as vasodilator agents. The most interesting vasodilators were the thiourea derivatives 6a and 6b and the urea derivatives 6f–6i and 7f–7h, although the ureas were relatively more active than thioureas. Twenty-fold more active than diazoxide, the urea 6g was the most potent vasodilator (EC50 = 0.983 ± 0.061 μmol/L) and proved to act as a voltage-gated calcium channel blocker. The lack of activity of sulfonylureas, 6k and 7j, could be attributed to their partial ionization at the physiological pH because of their acidic character. It should be interesting to investigate a larger number of compounds, including N-methylated sulfonylureas, to increase the vasodilator activity and to explore other biological models.