School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Bioorg Med Chem. 2013 Jul 1;21(13):3882-93. doi: 10.1016/j.bmc.2013.04.010. Epub 2013 Apr 18.
A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation.
设计、合成并评价了一系列在酚羟基位置带有不同酯和醚侧链的新型牛蒡子苷元和 9-去氧牛蒡子苷元衍生物，以评估它们在 L6 成肌细胞中激活 AMPK 的效力。初步的生物学评价表明，一些烷基酯和苯乙基醚牛蒡子苷元衍生物在改善 AMPK 磷酸化方面显示出潜在的活性。进一步的构效关系分析表明，牛蒡子苷元酯衍生物 3a、3h 和 9-去氧牛蒡子苷元苯乙基醚衍生物 6a、6c、6d 比牛蒡子苷元更能有效地激活 AMPK。此外，6c 的 2-(3,4-二甲氧基苯基)乙基醚部分已被证明是一个潜在的功能基团，可以改善 AMPK 磷酸化的效果。牛蒡子苷元的结构优化导致了 6c 的鉴定，它作为一种有前途的先导化合物，在 AMPK 激活方面表现出优异的活性。
