Chemical constituents of Himantormia lugubris collected from Antarctica and their PTP1B and α-glucosidase inhibitory activities

A phytochemical investigation of an Antarctic endemic species [Himantormia lugubris (Hue) M. Lamb] led to the isolation and structural elucidation of three new compounds including one lanostane-type triterpenoid (1, himanlugubrol A), one ergostane-type sterol (2, himanlugubrol B), one benzyl orsellinate derivative (3, himanlugubrin A), along with ten known compounds (4−13). The chemical structures of new compounds were determined using diverse NMR techniques, HRESIMS data analysis, and computational approaches supported by advanced statistics (DP4+). The anti-diabetic potential of all isolated compounds was investigated by evaluating their inhibitory effects on PTP1B and α-glucosidase enzymes. As a result, compound 3 moderately inhibited PTP1B with an IC₅₀ value of 43.86 µM and significantly inhibited α-glucosidase (IC₅₀ = 73.46 µM) in comparison to the positive controls, ursolic acid (IC₅₀ = 5.92 µM) and acarbose (IC₅₀ = 210.11 µM), respectively. Enzyme kinetic analysis revealed that compound 3 demonstrated noncompetitive inhibition of PTP1B and mixed-type inhibition of α-glucosidase. Additionally, molecular docking results supported these in vitro findings, showing that compound 3 had strong binding affinities for the active sites of both PTP1B and α-glucosidase, indicated by the key H-bond and van der Waals interactions and negative binding energies.