Four Undescribed Oxygenated Cardiac Glycosides From the Fruits of Thevetia peruviana With Their Anticancer Activities

ABSTRACT Phytochemical investigation of the extract from Thevetia peruviana fruits resulted in the isolation of 20 cardiac glycosides ( 1–20 ), including four previously undescribed compounds ( 1–4 ). Their chemical structures were elucidated through comprehensive spectroscopic analyses and quantum chemical calculations. Structurally, compounds 1‐4 are neriifolin derivatives featuring an additional hydroxyl group at C‐7 ( 1 and 2 ), C‐17 ( 3 ), and C‐4 ( 4 ) on the aglycone structure, respectively, were identified for the first time in the genus Thevetia . All the isolates were tested for their cytotoxic activities against four human cancer cell lines (MCF‐7, HCT‐116, HeLa, and HepG2), and their structure‐activity relationships were investigated. Of the four previously undescribed compounds, compound 1 demonstrated the strongest cytotoxic effects, with IC 50 values ranging from 0.096 to 0.410 µM. Furthermore, compound 1 was found to induce both apoptosis and G2/M phase arrest in a dose‐dependent manner toward HepG2 cells.