Twenty-eight naturally occurring Cephalotaxus tropone analogues, including 19 previously undescribed ones, were identified from Cephalotaxus fortunei Hook. var. alpina H. L. Li and C. lanceolata K. M. Feng. The presence of the C20 cephinoids A-E revealed that these tropones were assigned to the norditerpenoids and were perhaps derived from labdane-type diterpenoids. These norditerpenoids showed excellent cytotoxicity against human cancer cells (IC, 20-0.1 μM) in vitro. The SAR (structure-activity relationship) analysis disclosed that the tropone moiety and the lactone ring were crucial structural features for the observed activities. Further SAR analyses led to a new candidate, cephinoid H, which demonstrated an inhibition of 49.0% by administration to zebrafish at a dose of 60.0 ng/mL, compared to cisplatin (DDP, 22.4%) at 15.0 μg/mL. These compounds might affect the NF-κB signaling pathway rather than binding to microtubules. Additionally, the isolated norditerpenoids showed almost equal anti-inflammatory activities compared to the positive control, MG132.
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