Abstract
In 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.
Highlights
Aerobic organisms form reactive oxygen species (ROS) as an unavoidable consequence of cell metabolism
4-carbethoxyl holds strong potential to be (Figure S1). These results indicated that C-4 carboxyethyl substitution improves the metabolic stability of daphnetin
Daphnetin was chosen as the lead compound and more than twenty derivatives were designed and synthesized by structural modification on C-3 and/or C-4 position of daphnetin
Summary
Aerobic organisms form reactive oxygen species (ROS) as an unavoidable consequence of cell metabolism. There is an equilibrium between the natural antioxidative defense system and ROS. When the equilibrium is disrupted, ROS can induce both cellular damage responsible for aging and various pathologies in humans, such as rheumatoid arthritis, diabetes, and cancer [1,2,3]. A variety of powerful natural antioxidants have been identified that act as chemopreventive agents, which could prevent cancer through the action of antioxidants [4]. These compounds could exert anti-mutagenicity, anti-carcinogenicity, and anti-aging properties, which are thought to originate from their antioxidant activities [5]. With the goal of searching for antioxidant components, the structure-activity relationships of some natural compounds have been
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
