Diterpenoids from Cephalotaxus fortunei var. alpina and their cytotoxic activity.

• Fourteen diterpenoids were isolated from Cephalotaxus fortunei var. alpina. • Novel cephalotane-type diterpenoids with CH 3 -17 migrating to C-15 and C-13 were found. • 5 – 11 exhibited different degree of cytotoxicity against four human cancer cell lines. • 6 displayed stronger cytotoxicity against PC-3 cancer cells than etoposide. Cephafortunoids A–D (1 – 4), four new compounds, together with ten known ones (5 – 14), were isolated from the branches and leaves of Cephalotaxus fortunei var. alpina. 1 and 2 represent the first examples of Cephalotaxus troponoid diterpenoids featured an intact C 20 skeleton with CH 3 -17 migrating to C-15 and C-13 respectively. 3 and 4 are novel cephalotane-type diterpenoids with an epoxy ring between C-12 and C-13. The structures of isolated compounds were established by extensive spectroscopic methods, electronic circular dichroism (ECD) calculations, and comparison with reported data. In in vitro bioassays, all isolated compounds were evaluated for their cytotoxic activities against human promyelocytic leukemia cells (HL-60), human acute monocytic leukemia cells (THP-1), human breast cancer cells (MDA-MB-231), and human prostate cancer cells (PC-3). 5 – 9 exhibited prominent cytotoxicity against HL-60 and THP-1 with GI 50 values of 0.27–5.48 and 0.48–7.54 μM, respectively. 5 – 8 showed evident cytotoxicity against MDA-MB-231 and PC-3 with IC 50 values of 1.96–10.66 and 2.72–13.99 μM, severally. 6 with an IC 50 value of 2.72 ± 0.35 μM displayed stronger cytotoxicity against PC-3 than the positive control etoposide. The structure-activity relationship of these compounds and plausible biogenetic pathways for 1 – 4 were discussed. [ABSTRACT FROM AUTHOR]