Fourteen undescribed cassaine diterpenoids along with nine known ones were isolated from the seeds of Erythrophleum fordii Oliv. (Leguminosae). Besides, 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 anti-angiogenic activity using the human umbilical vein endothelial cells (HUVECs) model. Five of them were active, of which three compounds possessed excellent activity as their effect were 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 angiogenesis processes including proliferation, migration and capillary-like structure formation of endothelial cells. These findings may provide a new type of anti-angiogenic agents for future cancer drug development.Copyright © 2022. Published by Elsevier Ltd.