Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities

One new ent-kaurane diterpenoid, 11β,16α-dihydroxy-ent-kauran-19-oic acid (1), together with eight known analogues 2 - 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic diterpenoids, kaurenoic acid (3), was converted to seven derivatives, 10 - 16. All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG-2), and stomach (SGC-7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 - 16, with 15-keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC₅₀ value ranging from 0.05 to 3.71 μm. Compounds 10 - 12, with oxime on C(15) showed moderate inhibitory effects and compounds 1 - 9 showed no cytotoxicities on them. Structure-activity relationships were also discussed based on the experimental data obtained. The known derivative, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.