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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。
Prenylflavonoids are mainly distributed in legumes and mulberry plants, which have many biological activities. We previously reported that isoangustone A (IAA), derived from licorice, induces colon cancer cell apoptosis by disrupting mitochondrial function. In this paper, we compared the antiproliferative activities and the intracellular signaling pathways of other flavonoids and IAA from licorice and found that the isopentenyl groups on A and B rings are important contributors to their activity, while the ortho-positions Phenolic hydroxyl and C-ring conjugate plane also has some influence. In addition, these prenyl flavonoids cause PARP-1 cleavage, increased phosphorylation of AMPK and ACC, decreased phosphorylation of mTOR and 4EBP1, and activation of autophagy signaling. Based on the above preliminary structure-activity relationship studies, we also found from the licorice four other isopentenyl flavonoids also have strong antitumor activity. In this study, the structure-activity relationship of prenylflavonoids was preliminarily established, and their effects on intracellular signal were studied. Some leading compounds worthy of further study were found from licorice root.