Sesquiterpenoid glycosides from <i>Pittosporum kerrii</i> craib inhibit HT-29 colon cancer cells by apoptosis induction and down-regulation of CDK2

Six eudesmane-type sesquiterpenoid glycosides, including one previously undescribed one, pitkercoside A (<b>1</b>), five known analogs, pitsubcosides A, B, K, L (<b>2</b>-<b>5</b>), and pittosporam A (<b>6</b>) were discovered from <i>Pittosporum kerrii</i> Craib. The comprehensive spectroscopic technologies and chemical methods were applied to elucidate the structures of the compounds. Calculated electronic circular dichroism (ECD) technology was applied to determine the absolute configuration of the novel compound (<b>1</b>). Among them, compound <b>4</b> (pitsubcoside K, abbreviated as <b>PS-K</b>) exhibited a significant inhibitory effect on HT-29 cellular line with an IC₅₀ value of 4.43 <i>μ</i>M. It could up-regulate CHK2 and cause Cdc25A up-regulating, resulting in down-regulating CDK2 expression, which could regulate S-phase progression and cause S-phase arrest. Protein-molecule docking results suggest that PS-K has a strong tendency for spontaneous binding with ATM protein. This study revealed the effective metabolites and molecular mechanisms of <i>P. kerrii</i>, which enlarged the application of the plants of genus <i>Pittosporum</i>.