Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation
Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation
复制标题
DOI：
10.1016/j.bmc.2012.09.029
复制
发表时间：
2012-11-15
影响因子：
3.5
通讯作者：
Song, Dan-Qing
中科院分区：
文献类型：
--
作者：
Wang, Yan-Xiang;Kong, Wei-Jia;Song, Dan-Qing
目前还没有批准的药物用于治疗代谢综合征。合成了一系列新的小檗碱（BBR）或拟小檗碱（1）衍生物，并分别评价了它们对AMP活化蛋白激酶（AMPK）激活和上调低密度脂蛋白受体（LDLR）基因表达的活性。此外，还检查了体内BBR的四种主要代谢产物对AMPK的活性，以进一步了解其降糖功效的化学机制。在这些BBR类似物中，与BBR相比，化合物1表现出对AMPK活化和LDLR上调的潜在作用。结果表明，化合物1可能是一种治疗代谢综合征的多靶点药物，因此被选为一个有前途的候选药物进行进一步开发。(C)2012爱思唯尔有限公司保留所有权利。
Currently there is no approved medicine for the treatment of metabolic syndrome. A series of new derivatives of berberine (BBR) or pseudoberberine (1) was synthesized and evaluated for their activity on AMP-activated protein kinase (AMPK) activation and up-regulatory low-density-lipoprotein receptor (LDLR) gene expression, respectively. In addition, the four major metabolites of BBR in vivo were also examined for their activity on AMPK in order to further understand the chemical mechanisms responsible for its glucose-lowering efficacy. Among those BBR analogues, compound 1 exhibited the potential effect on AMPK activation and LDLR up-regulation as compared with BBR. The results suggested that compound 1 might be a multiple-target agent for the treatment of metabolic syndrome, and thus was selected as a promising drug candidate for further development. (C) 2012 Elsevier Ltd. All rights reserved.