Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko.
J Agric Food Chem
; 68(41): 11434-11448, 2020 Oct 14.
Article
in English
| MEDLINE | ID: covidwho-1301138
ABSTRACT
The dried fruits of Amomum tsao-ko 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 (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Plant Extracts
/
Amomum
/
Flavanones
/
Protein Tyrosine Phosphatase, Non-Receptor Type 1
/
Fatty Alcohols
/
Glycoside Hydrolase Inhibitors
/
Hypoglycemic Agents
Limits:
Humans
Language:
English
Journal:
J Agric Food Chem
Year:
2020
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS