Betulinic acid and its derivatives as anti-angiogenic agents

Betulinic acid (1) significantly caused cytotoxicity to endothelial cell line ECV304 (IC(50) 1.26+/-0.44 microg/mL) in a 5-day MTT assay. Novel and more potent derivatives of betulinic acid (2, 4, 6-8) have been synthesized with IC(50) less than 0.4 microg/mL. The endothelial cell specificity against human tumor cell lines DU145, L132, A549, and PA-1 were determined. Further betulinic acid (1) inhibited TLS formation of ECV304 cells on Matrigel(TM) by 5.5% while its derivatives caused an inhibition of 13.1-49.2%.