Evaluation of chelating agents as anti-angiogenic therapy through copper chelation

The evaluation of several sets of polyamine donor chelating agents including a selection of novel hexadentate 1,3,5-cis,cis-triaminocyclohexane (tach) based derivatives were performed in an in vitro endothelial cell proliferation assay to assess their cytotoxicity and selectivity as novel anti-angiogenic agents. The selective nature of the anti-angiogenic agents for human umbilical vein endothelial cells (HUVEC) was compared to a normal fibroblast cell line and a human Glioma cell line to evaluate these compounds. Linear tri- and tetra-polyamines were superior to both macrocyclic and the tach based polyamine chelating agents in terms of selectivity of its inhibitory activity toward the proliferation of HUVEC cells compared to the fibroblast and human Glioma cells. The linear polyamine, triethylenetetramine (22), previously reported to possess anti-angiogenic properties failed to demonstrate any selectivity for inhibiting the proliferation of HUVEC cells compared to the fibroblast and human Glioma cells.