Crotonianoids A–C, Three Unusual Tigliane Diterpenoids from the Seeds of Croton tiglium and Their Anti-Prostate Cancer Activity

Crotonianoids A–C (1–3), three unusual tigliane diterpenoids, were isolated from the seeds of Croton tiglium. Compound 1 is a 13,14:13,15-diseco-tigliane featuring a unique spiro[bicyclo[5.3.0]decane-2,5′-2′(3′H,4′H)-furanone] core; 2 is a 13,15-seco-tigliane incorporating a rare peroxide bridge between C-13 and C-15; and 3 is the first example of a phorbol ester with a 10R-configuration. Their structures were determined by spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 markedly inhibited the growth and survival of prostate cancer cell C4–2B at micromolar concentrations and induced cell apoptosis. Mechanistic study revealed that 1 and 2 could suppress androgen receptor (AR) signaling pathway by promoting the degradation of AR protein.