Selective Inhibition of PTP1B by New Anthraquinone Glycosides from .

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (-) and two known ones ( and ). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC values ranging from 1.05 to 13.74 μM. Compounds and exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds and behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.