Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and Their in Vitro PTP1B Inhibitory Activities

Six new and four known dihydrochalcone glucoside derivatives (1–10), the phenylpropanoid coniferin (11), and the lignans (+)-pinoresinol (12) and lariciresinol (13) were isolated from the subaerial plant parts of Thonningia sanguinea in the course of a screening campaign for new antidiabetic lead compounds. The structures of the new substances were elucidated by HRESIMS, NMR, GC-MS, and ECD data evaluation. 2′-O-(3-Galloyl-4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)-3-hydroxyphloretin (4), 2′-O-(4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (5), 2′-O-(3-O-galloyl-4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (6), and thonningianin B (9) showed moderate protein tyrosine phosphatase-1B inhibition in an enzyme assay (IC50 values ranging from 19 to 25 μM), whereas thonningianin A (10) was identified as a more potent inhibitor (IC50 = 4.4 μM). The observed activity differences could be explained by molecular docking experiments. The activity of 10 could further be confirmed in HEPG2 liver carcinoma cells, where the compound was able to increase the level of phosphorylated insulin receptors in a concentration-dependent manner.