Terpenoids and steroids from aerial parts of Achillea alpina L. as PTP1B inhibitors: Kinetic analysis and molecular docking studies

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1–8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC₅₀ values ranging from 14.87 to 23.09 μM in comparison with positive control - ursolic acid, showing IC₅₀ value of 5.93 ± 0.16 μM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action.