Synthesis and biological evaluation of thiobarbituric acid derivatives as antioxidant and cytotoxic agents

Oxidative stress (OS) arises from an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses of the body. Factors such as poor dietary patterns, exposure to environmental pollutants, and inappropriate self-medication aggravate this imbalance, thereby contributing to the onset and progression of diverse pathological conditions, including cancer, cardiovascular disorders (CVD), diabetes mellitus, and neurodegenerative disorders. This study aimed to synthesize and structurally characterize a series of twenty-eight thiobarbituric acid derivatives 1–28 and to evaluate the antioxidant and cytotoxic potential to identify safe and effective antioxidant agents. Thiobarbituric acid derivatives 1 - 28 were synthesized, and their structures were elucidated using EI-MS and ¹H NMR spectroscopy. Antioxidant activity was assessed using in vitro 1,1-diphenyl-1-picrylhydrazyl (DPPH) and superoxide anion radical (SOR) scavenging assays. Cytotoxicity was determined in PC3 prostate cancer cells employing the MTT assay. Several derivatives demonstrated significant antioxidant activity, with DPPH IC₅₀ values ranging from 22.5 to 214.8 µM. Compound 11 , bearing an ortho-trihydroxy substitution, showed the most potent activity in both bioassays, with IC₅₀ = 22.5 ± 1.1 µM in DPPH; 46.8 ± 1.5 µM in SOR. Most compounds exhibited minimal to no cytotoxicity at a concentration of 30 µM. Thiobarbituric acid derivatives 1 - 28 demonstrated promising antioxidant activity with no cytotoxicity, indicating their potential in managing oxidative stress–related disorders. However, further investigations using in vivo animal models are required to elucidate their molecular mechanisms of action and validate their therapeutic applications.