Cytotoxic macrocyclic diterpenoids from Jatropha multifida

Nine new macrocyclic diterpenoids (1-9), jatromultones A-I, along with eight known analogues (10-17) were isolated from the trunks of Jatropha multifida. The structures of the new compounds, including their absolute configurations, were elucidated by combination of spectroscopic analysis, single crystal X-ray diffraction, Rh-2(OCOCF3)(4) -induced CD method, and chemical correlations. All compounds were screened for the cytotoxicity against five cancer cell lines, including one drug-resistant cell line, and seven compounds exhibited significant activity with IC(50 )values less than 10 mu M. Compound 4 with IC50 values ranging from 2.69 to 6.44 mu M toward all cell lines was selected for further mechanistic study, which showed that 4 could arrest cell cycle at G2/M phase and induce apoptosis. The brief structure-activity relationships (SARs) of these macrocyclic diterpenoids were also discussed.