Sesquiterpenoids from Carpesium abrotanoides with structural diversity and anti-NSCLC activity

Phytochemical investigation of the branches and leaves of Carpesium abrotanoides led to the isolation of 28 sesquiterpenoids, including five new ones, carpabrotanes A–E ( 1 – 5 ). Their structures were elucidated by comprehensive spectroscopic analysis (NMR, HRESIMS, ECD) and single-crystal X-ray diffraction. Carpabrotanes A ( 1 ) and B ( 2 ) represent rare 13- nor -germacrane and 13- nor -pseudoguaiane sesquiterpenoids, respectively. All isolates were evaluated for their cytotoxicity against the non-small cell lung cancer (NSCLC) cell line NCI-H1975. Compounds 13 and 25 exhibited potent inhibitory activity, with IC 50 values of 3.68 ± 0.08 μM and 0.93 ± 0.02 μM, respectively, surpassing the positive control gefitinib (IC 50 = 9.27 ± 0.88 μM). Further mechanistic study on the selected compound ( 13 ) revealed that it induced S-phase cell cycle arrest and promoted apoptosis, as evidenced by downregulation of Cyclin A1, CDC2, and c-MYC, and upregulation of cleaved-PARP.