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Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumor progression. Synthetic derivatives of anti-cancer compound, noscapine (an opium alkaloid) such as Cl-noscapine, Br-noscapine and Folate-noscapine along with two of the reference compounds, TNP-470 and paclitaxel were examined for anti-angiogenic activities by using human umbilical vein endothelial cells (HUVECs). The noscapine derivatives showed anti-angiogenic activity albeit at high concentration compared to the reference compounds. All the tested compounds inhibited angiogenesis in a dose-dependent manner; the drug concentration causing 50% inhibition of cell survival was 11.87 μM for Cl-noscapine, 6.9 μM for Br-noscapine and 6.79 μM for folate-noscapine. Besides, all the noscapine derivatives significantly inhibited cord formation (IC50 for Cl-noscapine is 50.76 μM, for Br-noscapine is 90.08 μM and for folate-noscapine is 18.44 μM) as well as migration and invasion (IC50 value of Cl-noscapine is 28.01 μM, for Br-noscapine is 19.78 μM and for folate-noscapine is 10.76 μM) of endothelial cells. Based on these results, we speculated that the inhibitory effects on human endothelial cell proliferation of noscapine derivatives might be important for anti-angiogenesis.

Comparative evaluation of anti-angiogenic effects of noscapine derivatives