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Reactive oxygen species (ROS) cause oxidative damage to cellular membranes and macromolecules leading to diseases such as cancer. Antioxidants are chemical substances that scavenge free radicals and ROS and can be used as an alternative therapeutic approach to treat these diseases. In this work, we evaluate the in vitro antioxidant activity of a series of thiohydantoins, which five derivatives showed promising radical scavenging ability against stable DPPH (%I=90). The IC50 values ranged between 100 and 270 μM, and the best antioxidant potential was observed to thiohydantoin containing imidazole group in the side chain (IC50=40.0 μM). Kinetics analysis of the antioxidant activity indicated fast, intermediary, and slow behavior, while quantum calculations showed that the lowest IC50 is related to the best donating‐electron ability of the molecule. The molecular docking study for the best derivates against five relevant targets involved in the redox homeostasis: CP450, LOX, MPO, NOX, and XOX, suggest that the thiohydantoin ring acts as a pharmacophoric group in interactions with catalytic residues in the active site, demonstrating that thiohydantoin containing imidazole group in the side chain can be a promising compound as antioxidant agent. [ABSTRACT FROM AUTHOR]

DFT calculations were used to obtain parameters compatible with the CHARMM36 force field for iron-sulfur clusters (Fe-S) of the type [Fe 4 S 4 ] 2+ that are coordinated to dissimilatory adenosine-5'-phosphosulfate reductase (APSrAB). Classical molecular dynamics (MD) simulations were performed on two APSrAB systems to validate the parameters and verify the stability of the studied systems. The time analysis of the parameters inserted into the force field was in reasonable agreement with the experimental X-ray diffraction data. The analysis of the time evolution of the studied systems indicated that these systems and, in particular, the clusters in their respective cavities had a good stability and were in agreement with what was observed in previous works. The parameters obtained provide the basis for the study of APSrAB as well as other systems that contain [Fe 4 S 4 ] 2+ through the CHARMM36 force field.