Prenylated flavonoids from Glycyrrhiza uralensis as promising anti-cancer agents: a preliminary structure-activity study  

甘草中异戊烯基黄酮类化合物抗肿瘤活性构效关系初步研究（英文）

作　　者：唐叔南 黄维[1] 季帅[2] 王永瑞[1] 裴道勇 叶敏[2] 余四旺[1] 

机构地区：[1]北京大学医学部药学院化学生物学系,北京100191 [2]北京大学医学部药学院天然药物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2016年第1期23-29,共7页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81472657 and 81272468)

摘　　要：Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A（IAA） from licorice（Glycyrrhiza uralensis）, which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.异戊烯基黄酮类化合物主要分布在豆科和桑科植物中,具有多种生物活性。我们之前报道了一个从甘草中得到的异戊烯基异黄酮isoangustone A(IAA)可以通过破坏线粒体功能诱导结肠癌细胞凋亡。本文比较了来自甘草的其它一些结构相近的黄酮类化合物和IAA的抗增殖活性和对胞内信号通路的影响,发现A和B环上的异戊烯基对其活性有重要贡献,而邻位酚羟基和C环共轭平面也有一定影响。此外,这些异戊烯基黄酮类化合物可以导致PARP-1切割、AMPK和ACC磷酸化增加、m TOR和4EBP1磷酸化降低,并激活自噬信号。基于以上的初步构效关系研究,我们还从甘草中发现了另外4个异戊烯基黄酮类化合物也具有较强的抗肿瘤活性。本研究初步建立了异戊烯基黄酮类化合物的构效关系,研究了它们对胞内信号的影响,并从甘草中发现了一些值得进一步研究的先导化合物。

关 键 词：Prenylated flavonoids LICORICE ANTI-CANCER Structure-activity relationship 

分 类 号：R284[医药卫生—中药学]