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

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 mu M. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound (4) as the lead compound. Compound 4I (IC50 = 3.12 +/- 0.18 mu M) was 4.4-fold more potent than the lead compound 4 (IC50 = 13.72 +/- 1.53 mu M), and more potent than the positive control, ursolic acid (IC50=3.40 +/- 0.21 mu M). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.