Enantiomeric 3-arylcoumarins and 2-arylcoumarones from the roots of Glycyrrhiza uralensis as protein tyrosine phosphatase 1B (PTP1B) inhibitors

RSC Advances ◽  
2015 ◽  
Vol 5 (56) ◽  
pp. 45258-45265 ◽  
Author(s):  
Shuai Ji ◽  
Xue Qiao ◽  
Zi-wei Li ◽  
Yong-rui Wang ◽  
Si-wang Yu ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Glycyrrhiza Uralensis ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ptp1b Inhibitors ◽  
The Absolute

Four new PTP1B inhibitors were isolated from Glycyrrhiza uralensis, and the absolute configuration of 2,3-dihydro-2,3,3-trimethylbenzofurans was first unambiguously established.

scholarly journals Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Xiangyu Zhang ◽  
Hailun Jiang ◽  
Wei Li ◽  
Jian Wang ◽  
Maosheng Cheng
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Active Sites ◽  
Tyrosine Phosphatase ◽  
Pharmacophore Model ◽  
Protein Tyrosine Phosphatase 1B ◽  
Binding Modes ◽  
Protein Tyrosine ◽  
R Region ◽  
Ptp1b Inhibitors ◽  
Autodock 4.0

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors from Morinda citrifolia (Noni) and Their Insulin Mimetic Activity

2013 ◽  
Vol 76 (11) ◽  
pp. 2080-2087 ◽  
Author(s):  
Phi-Hung Nguyen ◽  
Jun-Li Yang ◽  
Mohammad N. Uddin ◽  
So-Lim Park ◽  
Seong-Il Lim ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Morinda Citrifolia ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Insulin Mimetic ◽  
Ptp1b Inhibitors

scholarly journals Correlation Between Nasal Epithelial Injury and In Vitro Cytotoxicity Using a Series of Small Molecule Protein Tyrosine Phosphatase 1B Inhibitors Investigated for Reversal of Leptin Resistance in Obesity

2017 ◽  
Vol 36 (4) ◽  
pp. 303-313
Author(s):  
Alan P. Brown ◽  
Chandrassegar Saravanan ◽  
Patrick Devine ◽  
Maria Magnifico ◽  
Jiaping Gao ◽  
...  
Keyword(s):  
Food Consumption ◽  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Sodium Dodecylbenzene Sulfonate ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Nasal Injury ◽  
Ptp1b Inhibitors

This research provides a cautionary example when evaluating changes in behavioral end points with respect to postulated pharmacologic activity. Various small molecule substrate mimetic protein tyrosine phosphatase 1B (PTP1B) inhibitors were investigated as pharmacologic agents for decreasing food consumption using intranasal (IN) dosing as a means for direct nose-to-brain delivery along the olfactory/trigeminal nerve pathways. Although food consumption was decreased in diet-induced obese (DIO) mice, nasal discharge was observed. Studies were conducted to investigate local effects on the nasal airway and to develop structure–activity relationships. Intranasal administration of PTP1B inhibitors at ≥0.03 mg/d to DIO mice produced dose-dependent injury to various cell types of the nasal epithelia. Protein tyrosine phosphatase 1B inhibitors with calculated log octanol >3.0 were the most toxic. Whereas a pharmacologically inactive analog of a PTP1B inhibitor produced nasal injury, along with decreased food consumption, the marketed IN drug ketorolac produced no lesions at the same dose of 0.3 mg/d and only minor changes at 3 mg/d. Rat skin fibroblast cells were exposed in vitro to PTP1B inhibitors, ketorolac, paraquat, and the detergent sodium dodecylbenzene sulfonate (NDS) followed by measures of cytotoxicity. The most potent PTP1B inhibitors were similar to NDS, whereas ketorolac was the least toxic compound. Cytotoxic potency in vitro was similar to in vivo. In conclusion, PTP1B inhibitors injured nasal epithelium through a mechanism independent of PTP1B inhibition and likely due to nonspecific cytotoxicity such as disruption of the cell membrane. Decreased food consumption in DIO mice was due to toxicity rather than a pharmacologic mode of action.

Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors

2004 ◽  
Vol 14 (22) ◽  
pp. 5543-5546 ◽  
Author(s):  
Hongyu Zhao ◽  
Gang Liu ◽  
Zhili Xin ◽  
Michael D. Serby ◽  
Zhonghua Pei ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ptp1b Inhibitors
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