Synthesis of Coumarin Derivatives and Evaluation of Their Antioxidant Activities against Multiple Free Radicals

Coumarin and its derivatives exhibit diverse biological activities and have extensive applications in biomedicine. A series of coumarin derivatives (1–15) were designed and synthesized, among which eight compounds had not been reported previously. In particular, single crystals of compounds 8 and 10 were obtained and characterized by X-ray diffraction, which provided a molecular basis for analyzing their antioxidant activity. The antioxidant properties were evaluated through ‧OH scavenging assays, cyclic voltammetry (CV) assays, redox potential measurements, oxygen radical absorbance capacity (ORAC) tests, and in vivo reactive oxygen species (ROS) scavenging experiments using Caenorhabditis elegans (C. elegans). At the same time, density functional theory (DFT) calculations were also conducted to assist in the study of the antioxidant mechanism. IC50 values for ·OH scavenging were significantly lower than those of the positive control, vitamin C. Furthermore, ORAC assays showed moderate to excellent scavenging ability (with Trolox equivalents of 1.08 for compound 13). CV assays assessed the abilities to scavenge ‧O2−, with results consistent with ORAC experimental findings. In vivo antioxidant activities were further investigated using C. elegans. Finally, through multiple free-radical scavenging experiments and DFT calculations, the antioxidant mechanism of the compounds was elucidated. In conclusion, through structural modification and the comparison of activities, profound insights were obtained. This work thereby established both a theoretical framework and an experimental basis for the rational design of new antioxidants.