Diterpenoids from the roots of Croton crassifolius and their anti-angiogenic activity

Six diterpenoids (1–6) along with eleven known ones were isolated from the supercritical fluid extract of the roots of Croton crassifolius. All the isolates were evaluated for their anti-angiogenic activity using the zebrafish in vivo model. [Display omitted] •Six diterpenoids and eleven known ones were isolated from Croton crassifolius.•The anti-angiogenic activity of the isolated diterpenoids was evaluated.•Penduliflaworosin showed strong anti-angiogenic effect. Six diterpenoids [crassifolin J, K, L, M, N and O] along with eleven known ones were isolated from the supercritical fluid extract (SFE) of the roots of Croton crassifolius (Euphorbiaceae). Their structures were elucidated using spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR). The structure and stereochemistry of crassifolin J was confirmed by single-crystal X-ray diffraction analysis, and the absolute configurations of crassifolin K–M were determined by CD spectra. Twenty-three diterpenoids from this plant were screened for their anti-angiogenic activity using a wild-type zebrafish in vivo model. Four of the known compounds were active, of which penduliflaworosin possessed the best activity relative to the positive control (SU5416). Further study demonstrated that penduliflaworosin could inhibit vessel formation on Tg(fli1a:EGFP)y1-type zebrafish embryos.