Novel 2-Thiouracil-5-Sulfonamide Derivatives: Design, Synthesis, Molecular Docking, and Biological Evaluation as Antioxidants with 15-LOX Inhibition.

New antioxidant agents are urgently required to combat oxidative stress, which is linked to the emergence of serious diseases. In an effort to discover potent antioxidant agents, a novel series of 2-thiouracil-5-sulfonamides ( 4 - 9 ) were designed and synthesized. In line with this approach, our target new compounds were prepared from methyl ketone derivative 3 , which was used as a blocking unit for further synthesis of a novel series of chalcone derivatives 4a - d , thiosemicarbazone derivatives 5a - d , pyridine derivatives 6a - d and 7a - d , bromo acetyl derivative 8 , and thiazole derivatives 9a - d . All compounds were evaluated as antioxidants against 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H 2 O 2 ), lipid peroxidation, and 15-lipoxygenase (15-LOX) inhibition activity. Compounds 5c , 6d , 7d , 9b , 9c , and 9d demonstrated significant RSA in all three techniques in comparison with ascorbic acid and 15-LOX inhibitory effectiveness using quercetin as a standard. Molecular docking of compound 9b endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.