Novel indole derivatives containing a thiosemicarbazide moiety as potential antioxidant agents for fresh beef...

Oxidative stress is implicated in numerous pathological processes. Developing efficient, safe small-molecule antioxidants is of great medicinal interest. In this work, ten new indole derivatives bearing a thiosemicarbazide moiety (4a-4j) were synthesized and fully characterized by ¹H NMR, ¹³C NMR, and HRMS. In vitro antioxidant assays indicated that all target compounds showed obvious free radical scavenging potency. Among them, compound 2-(3-(1H-indol-3-yl)propanoyl)-N-(4-chlorophenyl)hydrazine-1-carbothioamide (4i) displayed the strongest in vitro ABTS radical scavenging activity with an IC₅₀ = 0.96 μg/mL, remarkably lower than that of vitamin C (1.87 μg/mL). Compound 4i also exhibited excellent in vitro DPPH scavenging efficiency (IC₅₀ = 2.95 μg/mL). Molecular docking and 100 ns molecular dynamics simulations predicted that compound 4i stably bound to the catalytic pocket of human peroxiredoxin 5 (PDB ID: 1HD2). Meanwhile, in silico ADMET and drug-likeness predictions suggested favorable physicochemical properties, acceptable safety, and compliance with Lipinski's rule of five. Furthermore, application in a raw beef patty model revealed that compound 4i effectively retarded myoglobin oxidation, suppressed pH elevation, and preserved red-color stability during refrigerated storage, exhibiting superior color-protection performance. Collectively, these findings highlight compound 4i as a promising dual-purpose candidate, deserving further investigation both as an antioxidant lead for drug discovery and as a potential protective agent for raw meat preservation, with additional enzyme-level and food-safety assessments required.