十九个新的黄烷醇-脂肪醇杂合体具有α-葡萄糖苷酶和 PTP1B 双重抑制作用：来自. 的一种不寻常的抗糖尿病成分
Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from .
机构信息
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Yunnan Key Laboratory of Natural Medicinal Chemistry, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.
University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
出版信息
J Agric Food Chem. 2020 Oct 14;68(41):11434-11448. doi: 10.1021/acs.jafc.0c04615. Epub 2020 Oct 2.
The dried fruits of were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which , , , , and exhibited obvious activity against α-glucosidase with IC values of 5.2-9.0 μM, 20-35 times stronger than that of acarbose (IC, 180.0 μM); meanwhile, , -, and were PTP1B/TCPTP-selective inhibitors with IC values of 56.4-80.4 μM, 2-4 times stronger than that of suramin sodium (IC, 200.5 μM). Enzyme kinetics study indicated that compounds , , , and were α-glucosidase and PTP1B mixed-type inhibitors with values of 13.0, 11.7, 2.9, and 5.3 μM and 142.3, 88.9, 39.2, and 40.8 μM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.
该植物的干果首次在浓度为 200mg/kg 时被发现对 db/db 小鼠具有降血糖作用。为了阐明其抗糖尿病成分，从该植物中分离并鉴定了 19 种新的黄烷醇-脂肪醇杂合体，即 tsaokoflavanols A-S ()。通过广泛的光谱数据和 ECD 计算对这些化合物进行了结构鉴定。大多数化合物均表现出对 α-葡萄糖苷酶和 PTP1B 的双重抑制作用，其中化合物 、 、 、 和 对 α-葡萄糖苷酶表现出明显的活性，IC 值为 5.2-9.0 μM，比阿卡波糖（IC 值为 180.0 μM）强 20-35 倍；同时，化合物 、 、 和 为 PTP1B/TCPTP 选择性抑制剂，IC 值为 56.4-80.4 μM，比苏拉明钠（IC 值为 200.5 μM）强 2-4 倍。酶动力学研究表明，化合物 、 、 和 为 α-葡萄糖苷酶和 PTP1B 的混合型抑制剂， 值分别为 13.0、11.7、2.9 和 5.3 μM 和 142.3、88.9、39.2 和 40.8 μM。对接模拟证明了半缩醛羟基、3,4-二羟基苯基的取向以及与 α-葡萄糖苷酶和 PTP1B 结合的烷基长度的重要性。
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