Synthesis and Biological Evaluation of Heterocyclic Ring-substituted Chalcone Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

Bulletin of the Korean chemical society

Li-Xin Gao¹  Jia Li¹  Wei Zhang¹  Zhen-Hua Chen¹  Qiang Shen¹  Liang-Peng Sun¹  Hu-Ri Piao¹ 

关键词: Chalcone;    Protein tyrosine phosphatase 1B;    Inhibitor;    SAR;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound (4) was first observed to have moderate inhibitory activity against PTP1B with an IC50 value of 13.72 ± 1.53 μM. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound (4) as the lead compound. Compound 4l (IC50 = 3.12 ± 0.18 μM) was 4.4-fold more potent than the lead compound 4 (IC50 = 13.72 ± 1.53 μM), and more potent than the positive control, ursolic acid (IC50 = 3.40 ± 0.21 μM). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

【 授权许可】

Unknown