Synthesis and Biological Evaluation of Hydroxylcoumarin Derivatives as Antioxidant Agents

In this study, esculetin(1) was chosen as a lead compound and some structural modifications were designed to explore the antioxidant activities of esculetin derivatives. Meanwhile, a convenient method for selective methylation of catechol coumarins with different bases was developed. Furthermore, a few 5,7-dihydroxylcoumarins were synthesized and 7-hydroxylcoumarins were employed in order to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated and compared with standard antioxidant Trolox by the 2,2'-diphenyl-1-picrylhydrazyl(DPPH) assay, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation(ABTS(+)) assay and ferric reducing antioxidant power(FRAP) assay. The results show that the catechol group is the key pharmacophore. Meanwhile, introducing electronegative groups at the C4 position of esculetin(1) may enhance the antioxidative capacity, while introducing a group containing nitrogen as a hydrogen bond acceptor at the C8 position may slightly reduce the antioxidative capacity. Among them, the most powerful antioxidants are compounds 5 and 7, which exhibit higher antioxidant activity than esculetin(1) in all assays.