Novel chromenedione derivatives displaying inhibition of protein tyrosine phosphatase 1B (PTP1B) from Flemingia philippinensis

被引：31

作者：

Wang, Yan ^{[1
]}

Yuk, Heung Joo ^{[2
]}

Kim, Jeong Yoon ^{[2
]}

Kim, Dae Wook ^{[2
]}

Song, Yeong Hun ^{[2
]}

Tan, Xue Fei ^{[2
]}

Curtis-Long, Marcus J. ^{[3
]}

Park, Ki Hun ^{[2
]}

机构：

[1] Qiqihar Univ, Coll Food & Biol Engn, Qiqihar 161006, Peoples R China

[2] Gyeongsang Natl Univ, Div Appl Life Sci Plus BK21, IALS, Jinju 660701, South Korea

[3] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 02期

关键词：

Flemingia philippinensis; Chromenedione derivatives; Protein tyrosine phosphatase 1B (PTP1B); Philippin A; B; C; MOGHANIA-PHILIPPINENSIS; ROOTS;

D O I：

10.1016/j.bmcl.2015.12.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein tyrosine phosphatase 1B (PTP1B) is an important target to treat obesity and diabetes due to its key roles in insulin and leptin signaling. The MeOH extracts of the root bark of Flemingia philippinensis yielded eight inhibitory molecules (1-8) capable of targeting PTP1B. Three of them were identified to be novel compounds, philippin A (1), philippin B (2), and philippin C (3) which have a rare 3-phenyl-propanoyl chromenedione skeleton. The other compounds (4-8) were known prenylated isoflavones. All compounds (1-8) inhibited PTP1B in a dose dependent manner with IC(50)s ranging between 2.4 and 29.4 mu M. The most potent compound emerged to be prenylated isoflavone 5 (IC50 = 2.4 mu M). In kinetic studies, chromenedione derivatives (1-3) emerged to be reversible, competitive inhibitors, whereas prenylated isoflavones (5-8) were noncompetitive inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：318 / 321

页数：4