Valeriaquinone A,a unique anthraquinone–coumarin hybrid with selective inhibition of PTP1B from Knoxia valerianoides

Valeriaquinone A(1),an unprecedented anthraquinone–coumarin hybrid,was isolated from the roots of Knoxia valerianoides.Its structure was determined by extensive spectroscopic analyses and X-ray diffraction.The plausible biosynthetic pathways for 1 were proposed.Compound 1 exhibited strong protein tyrosine phosphatase 1 B(PTP1 B)inhibition with high selectivity(>30 fold)over homologous T cell protein tyrosine phosphatase(TCPTP)potentially by binding to an allosteric site predicted by kinetic analysis and molecular docking.Moreover,compound 1 showed significant cytotoxic activities against three human hepatoma cell lines(HepG2,QGY-7703,and SMMC-7721)with half maximal inhibitory concentration(IC_(50))values of 1.39±0.2,10.34±2.09,and 5.56±0.47μmol/L,respectively.