Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii.
10.1016/S1875-5364(19)30004-4
- Author:
Xiang-Yu ZHANG
1
,
2
;
Wei LI
1
,
3
;
Jian WANG
1
,
4
;
Ning LI
5
;
Mao-Sheng CHENG
1
,
2
;
Kazuo KOIKE
6
Author Information
1. Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
3. Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan. Electronic address: liwei@phar.toho-u.ac.jp.
4. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jianwang@syphu.edu.cn.
5. Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
6. Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
- Publication Type:Journal Article
- Keywords:
Protein tyrosine phosphatase 1B;
Raspberry;
Rubus chingii;
Triterpene;
Ursane
- MeSH:
Enzyme Inhibitors;
chemistry;
metabolism;
Fruit;
chemistry;
Humans;
Kinetics;
Methanol;
chemistry;
Molecular Docking Simulation;
Molecular Structure;
Plant Extracts;
chemistry;
Protein Binding;
Protein Tyrosine Phosphatase, Non-Receptor Type 1;
antagonists & inhibitors;
metabolism;
Protein Tyrosine Phosphatases;
antagonists & inhibitors;
Rubus;
chemistry;
Structure-Activity Relationship;
Triterpenes;
chemistry;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(1):15-21
- CountryChina
- Language:English
-
Abstract:
Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes: ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.
