Synthesis and antioxidant activity of conjugates of hydroxytyrosol and coumarin

• Published in: Bioorganic chemistry Vol. 105; pp. 104427 - 104439
• Main Authors: Li, Wen-Bo, Qiao, Xue-Peng, Wang, Zi-Xiao, Wang, Shuai, Chen, Shi-Wu
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.12.2020; Elsevier
• Subjects: Antioxidant; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Conjugates; Coumarin; Free radical scavenging; Hydroxytyrosol; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; Hydroxytyrosol; Conjugates; Free radical scavenging; Antioxidant; Coumarin; APOPTOSIS; CELLS; OXIDATIVE STRESS; ROS
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104427

[Display omitted] •Twenty conjugates of coumarin and hydroxytyrosol were synthesized.•These conjugates showed potent antioxidant activities in DPPH and ABTS assays.•Compound 14q exhibited less toxicity and weaker cytotoxicity.•Compound 14q enhanced the cell viability of H2O2-injured HepG2 cells and WI-38 cells.•Compound 14q increased ROS, SOD and GSH, and reduced LDH in H2O2-treated HepG2 cells. Antioxidants have been the subject of intense research interest due to their numerous health benefits. In this work, a series of new conjugates of hydroxytyrosol and coumarin were synthesized and evaluated for their free radical scavenging, toxicity and antioxidant mechanism in vitro. The all target compounds 14a–t exhibited better radical scavenging activity than BHT, hydroxytyrosol, and coumarin in both DPPH radical and ABTS+ radical cation scavenging assays. The structure-activity relationships study indicated that the number and position of hydroxyl groups on the coumarin ring were vital to a good antioxidant capacity. Furthermore, the most promising compound 14q showed less toxicity in hemolysis assay and weaker antiproliferative effects than BHT against normal WI-38 and GES cells, and enhanced viability of H2O2-induced HepG2 cells. Additionally, 14q decreased the apoptotic percentage of HepG2 cells, reduced the ROS produce and LDH release, and improved GSH and SOD levels in H2O2-treated HepG2 cells. Lastly, 14q exhibited more stability than hydroxytyrosol in methanol solution. These results revealed that conjugations of hydroxytyrosol and coumarin show better antioxidant capacity, and are the efficacious approach to finding novel potential antioxidant.