3,5-Diarylpyrazole Derivatives Obtained by Ammonolysis of the Total Flavonoids from Chrysanthemum indicum Extract Show Potential for the Treatment of Alzheimer's Disease

作者：Wu, Taizong; Jiang, Cheng; Wang, Ling; Morris-Natschke, Susan L.; Miao, Hui; Gu, Lianquan; Xu, Jun; Lee, Kuo-Hsiung^*; Gu, Qiong

来源：Journal of Natural Products, 2015, 78(7): 1593-1599.

DOI：10.1021/acs.jnatprod.5b00156

• CHEMICALLY ENGINEERED EXTRACTS
• DISCOVERY
• INHIBITORS
• PEPTIDE

Four new 3,5-diarylpyrazole analogues (1-4) were isolated from an extract of the flowers of Chrysanthemun indicum using a combination of ammonolysis of the total flavonoid extract and an A beta aggregation inhibitory activity guided purification procedure. All four compounds (1-4) showed moderate to potent activity against A beta aggregation with EC50 values of 4.3, 15.8, 1.3, and 2.9 mu M, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against A beta-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit A beta aggregation and exhibit neuroprotective activity with potential for the treatment of Alzheimer's disease. Taken together, the method presented here offers an alternative approach to yield bioactive compounds.

• 出版日期2015-7
• 单位中国医科大学; 中山大学