PTP1B inhibitory activity of kaurane diterpenes isolated from Siegesbeckia glabrescens
PTP1B inhibitory activity of kaurane diterpenes isolated from Siegesbeckia glabrescens
复制标题
DOI：
10.1080/14756360600741560
复制
发表时间：
2006-08-01
影响因子：
5.6
通讯作者：
Ahn, Jong Seog
中科院分区：
文献类型：
--
作者：
Kim, Sohee;Na, Minkyun;Ahn, Jong Seog
蛋白酪氨酸磷酸酶1B(PTP1B)被认为是治疗糖尿病和肥胖症的靶点。在我们的初步筛选研究中，发现光肩星天牛地上部分的甲醇提取物在30 mg/mL时对PTP1B活性有抑制作用。分离得到两个活性二萜化合物：Et-16bH，17-异丁氧基-Kauran-19-OIC酸(1)和Et-16bH，17-乙酰氧基-18-异丁氧基-Kauran-19-OIC酸(2)，以及Et-16bH，17-羟基Kauran-19-OIC酸(3)。化合物1和2对PTP1B活性有抑制作用，IC50值分别为8.7+/-0.9和30.6+/-2.1mM。动力学研究表明，1和2都是PTP1B的非竞争性抑制剂。而在角叉烷型化合物中C-17位羟基取代的化合物3对PTP1B没有抑制作用。
Protein tyrosine phosphatase 1B (PTP1B) is considered as a therapeutic target for the treatment of diabetes and obesity. In our preliminary screening study, a MeOH extract of the aerial part of Siegesbeckia glabrescens was found to inhibit PTP1B activity at 30 mg/mL. Bioassay-guided fractionation led to the isolation of two active diterpenes, ent-16 beta H, 17-isobutyryloxykauran-19-oic acid (1) and ent-16bH, 17-acetoxy-18-isobutyryloxy-kauran-19-oic acid (2), along with ent-16bH, 17-hydroxykauran-19-oic acid (3). Compounds 1 and 2 inhibited the PTP1B activity with IC50 values of 8.7 +/- 0.9 and 30.6 +/- 2.1 mu M, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. However, compound 3 substituted with a hydroxyl group at C-17 in kaurane-type showed no inhibitory effects towards PTP1B.