Synthesis and Structure-Activity Relationship of Daphnetin Derivatives as Potent Antioxidant Agents
AbstractIn this study, daphnetin 1 was chosen as the lead compound, and C-3 or C-4-substituted daphnetins were designed and synthesized to explore the potential relationship between the antioxidant activities and the chemical structures of daphnetin derivatives. The antioxidant activities of the generated compounds were evaluated utilizing the free radical scavenging effect on 2,2′-diphenyl-1-picrylhydrazyl, 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation, and the ferric reducing power assays, and were then compared with those of the standard antioxidant Trolox. The results showed that the catechol group was the key pharmacophore for the antioxidant activity of the daphnetins. The introduction of an electron-withdrawing hydrophilic group at the C-4 position of daphnetin enhanced the antioxidative capacity, but this trend was not observed for C-3 substitution. In addition, introduction of a a hydrophobic phenyl group exerted negative effects on the antioxidant activity in both the C-3 and C-4 substitutions. Among all of the derivatives tested, the most powerful antioxidant was 4-carboxymethyl daphnetin (compound 9), for which the strongest antioxidant activity was observed in all of the assays. In addition, compound 9 also displayed strong pharmaceutical properties in the form of metabolic stability. To summarize, compound 9 holds great potential to be developed as an antioxidant agent with excellent antioxidant activity and proper pharmacokinetic behavior. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 2736 KB)
Share & Cite This Article
Xia, Y.; Chen, C.; Liu, Y.; Ge, G.; Dou, T.; Wang, P. Synthesis and Structure-Activity Relationship of Daphnetin Derivatives as Potent Antioxidant Agents. Molecules 2018, 23, 2476.
Xia Y, Chen C, Liu Y, Ge G, Dou T, Wang P. Synthesis and Structure-Activity Relationship of Daphnetin Derivatives as Potent Antioxidant Agents. Molecules. 2018; 23(10):2476.Chicago/Turabian Style
Xia, Yangliu; Chen, Chen; Liu, Yong; Ge, Guangbo; Dou, Tongyi; Wang, Ping. 2018. "Synthesis and Structure-Activity Relationship of Daphnetin Derivatives as Potent Antioxidant Agents." Molecules 23, no. 10: 2476.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.