Synthesis and biological evaluation of heterocyclic ring-substituted chalcone derivatives as novel inhibitors of protein tyrosine phosphatase 1B

Abstract

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. Copyright © 2005 KCSNET.