Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

Haibing He, Yinghua Ge, Hong Dai, Song Cui, Fei Ye, Jia Jin, Yujun Shi
2016 Molecules  
By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by 1 H-NMR, 13 C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had
more » ... d activities against PTP1B. Among them, compound 29 (IC 50 = 0.91 ± 0.33 µM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound 29 was identified as a competitive inhibitor of PTP1B with a K i value of 0.78 µM in enzyme kinetic studies. Molecules 2016, 21, 1722 2 of 11 in drug design when use the "scaffold hopping" method [15] . Additionally, stilbene is a common moiety found in many natural products endowed with antibacterial, antioxidative, antiproliferative or antidiabetic activities, such as resveratrol (6) , pinosylvin (7) and piceatannol (8) [16] [17] [18] [19] .
doi:10.3390/molecules21121722 pmid:27999292 fatcat:yvwts3av6vdddgqqtgva462hiy