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Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa
- Source :
- Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 32, Iss 1, Pp 1195-1202 (2017), Journal of Enzyme Inhibition and Medicinal Chemistry
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1–8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1–5) and dihydroflavonols (6–8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50 = 1.9–8.2 μM) than α-glucosidase (IC50 = 2.2–78.9 μM). Mimulone (1) was the most effective against PTP1B with IC50 = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC50 = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.
- Subjects :
- medicine.medical_treatment
Mixed type
Protein tyrosine phosphatase
Biology
01 natural sciences
Magnoliopsida
Structure-Activity Relationship
Non-competitive inhibition
Drug Discovery
medicine
Humans
Enzyme Inhibitors
enzyme inhibition
Flavonoids
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Pharmacology
chemistry.chemical_classification
Dose-Response Relationship, Drug
Molecular Structure
010405 organic chemistry
Leptin
α glucosidase
Insulin
lcsh:RM1-950
PTP1B
Paulowinia tomentosa
alpha-Glucosidases
General Medicine
biology.organism_classification
0104 chemical sciences
Paulownia tomentosa
010404 medicinal & biomolecular chemistry
lcsh:Therapeutics. Pharmacology
Enzyme
Biochemistry
chemistry
Fruit
kinetic analysis
α-glucosidase
hormones, hormone substitutes, and hormone antagonists
Research Paper
Subjects
Details
- ISSN :
- 14756374 and 14756366
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....bcfc35f7c0272245683a745b12281a3a