Mechanism of attenuation of diabetes mellitus and hypercholesterolemia induced vascular endothelial dysfunction by protein tyrosine phosphatase inhibition

2011 ◽  
Vol 54 (3-6) ◽  
pp. 80-87 ◽  
Author(s):  
Saurabh Sharma ◽  
Manjeet Singh ◽  
Pyare Lal Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Protein Tyrosine ◽  
Phosphatase Inhibition

scholarly journals In Search for Multi-Target Ligands as Potential Agents for Diabetes Mellitus and Its Complications—A Structure-Activity Relationship Study on Inhibitors of Aldose Reductase and Protein Tyrosine Phosphatase 1B

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 330
Author(s):  
Rosaria Ottanà ◽  
Paolo Paoli ◽  
Mario Cappiello ◽  
Trung Ngoc Nguyen ◽  
Ilenia Adornato ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Aldose Reductase ◽  
Protein Tyrosine Phosphatase ◽  
Complex Disease ◽  
Tyrosine Phosphatase ◽  
C2c12 Cell ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
In Silico Docking ◽  
Multiple Ligands

Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates.

Peroxynitrite and Vascular Endothelial Dysfunction in Diabetes Mellitus

Endothelium ◽  
2004 ◽  
Vol 11 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Ming-Hui Zou ◽  
Richard A. Cohen ◽  
Volker Ullrich
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction

Receptor-Type Protein-Tyrosine Phosphatase μ Is Expressed in Specific Vascular Endothelial Bedsin Vivo

1999 ◽  
Vol 248 (1) ◽  
pp. 329-338 ◽  
Author(s):  
Cesario Bianchi ◽  
Frank W. Sellke ◽  
Robert L. Del Vecchio ◽  
Nicholas K. Tonks ◽  
Benjamin G. Neel
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Receptor Type ◽  
Vascular Endothelial ◽  
Protein Tyrosine ◽  
Type Protein
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