Synthesis and biological evaluation of 2,4,6-trihydroxychalcone derivatives as novel protein tyrosine phosphatase 1B inhibitors

Abstract

A series of 2,4,6-trihydroxychalcone derivatives were synthesized and identified as reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with IC₅₀ values in the micromolar range. Compound 4a had the greatest in vitro inhibition activity against PTP1B (IC₅₀= 0.27 ± 0.01 μM) and the best selectivity (6.9-fold) for PTP1B relative to T-cell protein tyrosine phosphatases. The compounds identified herein provide a foundation on which to design specific inhibitors of PTP1B and other PTPs.