Cassaine diterpenoids from the seeds of Erythrophleum fordii Oliv. and their antiangiogenic activity

Fourteen undescribed cassaine diterpenoids along with nine known ones were isolated from the seeds of Erythrophleum fordii Oliv. (Leguminosae). In addition, subsequent structural modification yielded ten derivatives. Their chemical structures were established by extensive spectroscopic methods and acid hydrolysis. All the diterpenoids were screened for their antiangiogenic activity using the human umbilical vein endothelial cell (HUVEC) model. Five compounds were active, of which three possessed excellent activity as their effect was better than that of the positive control (SU5416). The structure-activity relationship analysis revealed that the side chain at C-13 was the key part affecting the inhibitory effect. Further study demonstrated that 3β-hydroxynorerythrosuamine-3-O-β-D-glucopyranoside and the formate of 3β-hydroxynorerythrosuamine-3-O-β-D-glucopyranoside significantly inhibited a series of angiogenic processes including proliferation, migration and capillary-like structure formation of endothelial cells. These findings may provide a new type of antiangiogenic agent for future cancer drug development. Fourteen cassaine diterpenoids along with nine known ones were isolated from the seeds of Erythrophleum fordii (Leguminosae). Beside, subsequent structural modification yielded ten derivatives. All the diterpenoids were evaluated for their antiangiogenic activity using in vitro model. [Display omitted] •Twenty-three cassaine diterpenoids were isolated from Erythrophleum fordii.•Ten derivatives of cassaine diterpenoids were synthesized.•All the diterpenoids were screened for their antiangiogenic activity.•The side chain at C-13 was the key part affecting the antiangiogenic activity.