Synthesis, In Vitro, and In Silico Analysis of the Antioxidative Activity of Dapsone Imine Derivatives

Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives - were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (, , and ). Likewise, we have three compounds with better reducing activity than dapsone (, , and ). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω/ω) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAP and DAM with the observed antioxidant effects. According to the results, we concluded that compounds and have the lowest values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives , , and display the best reducing capacity activity with the highest ω and values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.