Li Jin-Long, Gao Li-Xin, Meng Fan-Wang, Tang Chun-Lan, Zhang Ru-Jun, Li Jing-Ya, Luo Cheng, Li Jia, Zhao Wei-Min
Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Bioorg Med Chem Lett. 2015;25(10):2028-32. doi: 10.1016/j.bmcl.2015.04.003. Epub 2015 Apr 4.
Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.
从明日叶（Angelica keiskei Koidzumi）的茎中分离出三种新的查耳酮，即黄当归醇K-M（1-3），以及19种已知化合物。明日叶是一种源自日本的著名的具有回春功效和抗糖尿病作用的植物。基于光谱数据和莫舍尔方法阐明了化合物1-3的结构。对所有化合物进行了抗蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性的评估。其中，六种查耳酮，即黄当归醇K（1）、黄当归醇（4）、黄当归醇F（5）、4-羟基德里辛（6）、黄当归醇D（7）、黄当归醇E（8），以及一种香豆素，甲氧沙林（17），表现出较强的PTP1B抑制作用，IC50值分别为0.82、1.97、1.67、2.47、3.97、1.43和2.53μg/mL。动力学研究表明，化合物1以竞争性抑制剂的典型特征抑制PTP1B。分子对接模拟表明，化合物1的B环可能锚定在PTP1B的一个口袋中，并且该分子通过与PTP1B的Arg47、Asp48形成氢键以及与Phe182的π-π相互作用而稳定。
