PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic properties and molecular docking simulation

[Display omitted] •Four new compounds were isolated from the aerial parts of Selaginella tamariscina.•Isolates (1–7) were tested for their inhibitory effects on PTP1B enzymes.•These compounds were also evaluated for enzyme kinetic assay.•Molecular docking further confirmed the structures of 1–3 (S-form), and 4, 5 (R-form). Diabetes is one of the most popular worldwide diseases, regulated by the defects in insulin secretion, insulin action, or both. The overexpression of protein tyrosine phosphatase 1B (PTP1B) was found to down-regulate the insulin-receptor activation. PTP1B has been known as a strategy for the treatment of diabetes via the regulation of insulin signal transduction pathway. Herein, we investigated the PTP1B inhibitors isolated from natural sources. The chemical investigation of Selaginella tamariscina (Beauv.) Spring revealed seven unsaturated alkynyl phenols 1–7, four new selaginellins T–W 1–4 together with three known compounds 5–7 isolated from the aerial parts. The structures of the isolates were determined by spectroscopic techniques (1D/2D-NMR, MS, and CD). The inhibitory effects of these isolates on the PTP1B enzyme activity were investigated. Among them, compounds 2–7 significantly exhibited the inhibitory effects with the IC50 values ranging from 4.8 to 15.9μM. Compound 1 moderately displayed the inhibitory activity with an IC50 of 57.9μM. Furthermore, active compounds were discovered from their kinetic and molecular docking analysis. The results revealed that compounds 2 and 4–7 were mixed-competitive inhibitors, whereas compound 3 was a non-competitive inhibitor. This data confirm that these compounds exhibited potential inhibitory effect on the PTP1B enzyme activity.