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 1–10 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 (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). 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_HOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest R_a values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω⁻ and R_d values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.

Objective: The aim of this study was to determine the vasorelaxant effect of semisynthetic derivatives of ursolic acid, establish the mode of action, and determine the antihypertensive effect of the most active compound.Methods: Isolated aorta rat rings (ex vivo assay), with and without endothelium, were used to determine the vasorelaxant effect of seven semisynthetic derivatives of ursolic acid (UA-01 to UA-07). Then, the effect of the most active compound was studied in ex vivo assay using L-NAME, ODQ and indomethacin to determine its mode action. Finally, the in vivo cardiovascular effect and molecular docking of the most active compound were determined.Results: UA-07 was the most potent compound of the derivatives, since UA-07 induced significant relaxant effect in concentration- and endothelium-dependent manners (Emax = 79.09% and EC50 = 110 μM) on aortic rat rings pre-contracted with noradrenaline (NA, 0.1 μM). Also, endothelium-derived nitric oxide seems to be involved in the mechanism of action of UA-07, because pre-incubation with L-NAME (a NOS inhibitor) and ODQ (a soluble guanylate cyclase inhibitor) significantly reduced its vasorelaxant effect. Further, UA-07 showed a similar binding affinity as ursolic acid on eNOS C1 binding pocket in in silico studies. Finally, treatment with UA-07 (50 mg/Kg) on spontaneously hypertensive rats (SHR) significantly decreased diastolic blood pressure for seven hours.Conclusion: These results demonstrate the significant antihypertensive effect of UA-07, possibly through the NO/cGMP system.