†Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
‡Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
J Nat Prod. 2015 Jul 24;78(7):1593-9. doi: 10.1021/acs.jnatprod.5b00156. Epub 2015 Jun 23.
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 Aβ aggregation inhibitory activity guided purification procedure. All four compounds (1-4) showed moderate to potent activity against Aβ aggregation with EC50 values of 4.3, 15.8, 1.3, and 2.9 μM, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against Aβ-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit Aβ 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.
从菊花（Chrysanthemun indicum）花提取物中分离出四种新的 3,5-二芳基吡唑类似物（1-4），采用总黄酮提取物氨解和 Aβ 聚集抑制活性导向纯化程序的组合。所有四种化合物（1-4）对 Aβ 聚集均表现出中等至强的活性，EC50 值分别为 4.3、15.8、1.3 和 2.9 μM。此外，化合物 3 对 Aβ 诱导的 SH-SY5Y 细胞系细胞毒性具有低细胞毒性和显著的神经保护活性。本报告首次表明 3,5-二芳基吡唑类似物可以抑制 Aβ 聚集并具有神经保护活性，具有治疗阿尔茨海默病的潜力。综上所述，本文提出的方法提供了一种获得生物活性化合物的替代方法。
