Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
; (6): 15-21, 2019.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-776910
Responsible library:
WPRO
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.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Protein Binding
/
Structure-Activity Relationship
/
Triterpenes
/
Plant Extracts
/
Kinetics
/
Molecular Structure
/
Chemistry
/
Protein Tyrosine Phosphatases
/
Methanol
/
Enzyme Inhibitors
Limits:
Humans
Language:
English
Journal:
Chinese Journal of Natural Medicines (English Ed.)
Year:
2019
Document type:
Article