Evaluation of copper chelation agents as anti-angiogenic therapy

The design, synthesis and evaluation of N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5,-triaminocyclohexane (tachpyr, 1) derivatives as novel anti-angiogenic agents were performed in an in vitro endothelial cell proliferation assay to assess their cytotoxicity and selectivity. 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. N,N',N"-tris(2-mercaptoethyl)-cis,cis-1,3,5-triaminocyclohexane trihydrochloride (3b) was superior to tachpyr in terms of selectivity of its inhibitory activity toward the proliferation of Huvec compared to the fibroblast and human Glioma cell lines.