Synthesis, biological evaluation, and molecular docking study of novel allyl-retrochalcones as a new class of protein tyrosine phosphatase 1B inhibitors

2019 ◽  
Vol 27 (6) ◽  
pp. 963-977
Author(s):  
Yunjie Zhao ◽  
Yongkai Cao ◽  
Huizhen Chen ◽  
Fei Zhuang ◽  
Chao Wu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Docking Study ◽  
Biological Evaluation ◽  
Protein Tyrosine Phosphatase 1B ◽  
Molecular Docking Study ◽  
Protein Tyrosine ◽  
New Class

scholarly journals Structural Bases for Hesperetin Derivatives: Inhibition of Protein Tyrosine Phosphatase 1B, Kinetics Mechanism and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7433
Author(s):  
Md Yousof Ali ◽  
Susoma Jannat ◽  
Hyun-Ah Jung ◽  
Jae-Sue Choi
Keyword(s):  
Molecular Docking ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Docking Study ◽  
Docking Studies ◽  
Protein Tyrosine Phosphatase 1B ◽  
Allosteric Site ◽  
Molecular Docking Study ◽  
Protein Tyrosine ◽  
Diabetic Treatment

In the present study, we investigated the structure-activity relationship of naturally occurring hesperetin derivatives, as well as the effects of their glycosylation on the inhibition of diabetes-related enzyme systems, protein tyrosine phosphatase 1B (PTP1B) and α-glycosidase. Among the tested hesperetin derivatives, hesperetin 5-O-glucoside, a single-glucose-containing flavanone glycoside, significantly inhibited PTP1B with an IC50 value of 37.14 ± 0.07 µM. Hesperetin, which lacks a sugar molecule, was the weakest inhibitor compared to the reference compound, ursolic acid (IC50 = 9.65 ± 0.01 µM). The most active flavanone hesperetin 5-O-glucoside suggested that the position of a sugar moiety at the C-5-position influences the PTP1B inhibition. It was observed that the ability to inhibit PTP1B is dependent on the nature, position, and number of sugar moieties in the flavonoid structure, as well as conjugation. In the kinetic study of PTP1B enzyme inhibition, hesperetin 5-O-glucoside led to mixed-type inhibition. Molecular docking studies revealed that hesperetin 5-O-glucoside had a higher binding affinity with key amino residues, suggesting that this molecule best fits the PTP1B allosteric site cavity. The data reported here support hesperetin 5-O-glucoside as a hit for the design of more potent and selective inhibitors against PTP1B in the search for a new anti-diabetic treatment.

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