Opeturins I-XIV, structurally diverse resin glycosides from Operculina turpethum and their biological activities.

Fourteen previously undescribed resin glycosides, opeturins I-XIV (1-14), were isolated from the roots of Operculina turpethum using separation and purification techniques including extraction, column chromatography and preparative HPLC. Their structures were established by extensive spectroscopic analysis, including IR, HRESIMS, and NMR, along with chemical degradation. Compounds 1-6 were characterized as macrolactonic pentasaccharide resin glycosides bearing 24- or 22-membered rings, whereas compounds 7-14 were non-macrolactonic acylated glycosidic acids or their methyl esters with penta-, tetra-, or trisaccharide cores. All the compounds contained 11S-hydroxyhexadecanoic acid as the aglycone, together with 2S-methylbutanoyl, hexadecanoyl, or octadecanoyl substituents. Cytotoxic evaluation using the CCK8 assays revealed that compounds 1-3, 7, 8, 10 and 14 were cytotoxic to HepG2 or A549 cells with the IC50 values ranging from 6.58 to 49.76 μM. Among them, compounds 1 displayed most potent activity against HepG2 cells with the IC50 value of 6.58 ± 1.18 μM, and docking analysis predicted its binding within the established inhibitor-binding pocket of Sec61 with predicted binding energy of -5.2 kcal/mol. In addition, compound 12 inhibited both α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 48.83 ± 1.63 and 52.52 ± 6.67 μM, respectively, and docking analysis provided plausible binding modes for both enzymes with predicted binding energies of -7.2 and - 4.9 kcal/mol, respectively. These findings expanded the structural diversity known for resin glycosides from O. turpethum and identified compounds that merit further mechanistic evaluation.