Six selaginellin derivatives with protein tyrosine phosphatase 1B inhibitory activity from Selaginella tamariscina

As part of an ongoing search for new PTP1B inhibitors from medicinal plants, the methanol extract of the aerial parts of Selaginella tamariscina was found to inhibit 70% PTP1B enzyme activity at a concentration of 30 µg/mL. Thus, bioassay-guided isolation of this active extract yielded six selaginellin derivatives (1-6), comprising four new compounds (selariscinas A˜D; 2˜6). These compounds were found to possess inhibitory effect on PTP1B enzyme activity with IC₅₀ values ranging from 5.5 ± 0.1 to 21.6 ± 1.5µM. Furthermore, compound 2 which served as mixed-competitive inhibitor showed the greatest potency, with IC₅₀ value of 5.5 ± 0.1µM, when compared with the positive control (ursolic acid, IC₅₀= 3.4 ± 0.1). This result indicated the potential of these selaginellin derivatives as lead molecules for the development of antidiabetic agents and the beneficial use of S. tamariscina against hyperglycemia.