Design, synthesis and evaluation of antioxidant and anti-inflammatory activities of novel resveratrol derivatives as potential multifunctional drugs

• Published in: European journal of medicinal chemistry 2024-02, Vol.266, p.116148-116148, Article 116148
• Main Authors: Lu, Jia-Xun, Wang, Wei, Zhang, Qi-Wen, Guo, Zheng-Yan, Jin, Zhen, Tang, You-Zhi
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammation; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-oxidation; Antioxidants - therapeutic use; Humans; Hydrogen Peroxide - pharmacology; Inflammation - drug therapy; Lipopolysaccharides - pharmacology; Mice; Molecular hybridization; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidative Stress; RAW 264.7 Cells; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2024.116148

Oxidative stress and inflammation responses are closely related to the occurrence and development of many diseases. Therefore, anti-oxidation and anti-inflammation have become hot spots in the treatment of diseases. A series of novel resveratrol derivatives which hybrid with benzoylhydrazines were designed, synthesized and assessed for their in vitro antioxidant and anti-inflammatory activity. Initially, the antioxidant abilities of resveratrol derivatives were investigated by DPPH, ABTS radical scavenging and FRAP assays. RAW 264.7 macrophages are routinely used to evaluate the antioxidant and anti-inflammatory activities of drugs, so we used it to construct cell models of oxidative stress and inflammation. Among all the derivatives, compound 5 exhibited superior ROS- and NO-inhibitory activities. The molecular mechanism detected by Western blotting showed that compound 5 could significantly activate the Nrf2 signaling pathway and up-regulate the expression of HO-1 to resist oxidative stress stimulated by H2O2. At the same time, it could down-regulate the expression of apoptosis-related proteins Caspase3 and PARP, alleviating cells damage and apoptosis. In addition, compound 5 dose-dependently inhibited the activation of NF-κB p65/iNOS and MAPKs signaling pathway. [Display omitted] •Resveratrol derivatives were designed and synthesized by molecular hybridization approach.•Introduction of hydroxyl and amino groups to resveratrol derivatives could significantly enhance their free radical scavenging abilities.•Compound 5 exerted superior antioxidant and anti-inflammatory activities.