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.
Camphausen
Kevin
K
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room B3B69, Bethesda, MD 20892-1002, USA.
Sproull
Mary
M
Tantama
Steve
S
Sankineni
Sandeep
S
Scott
Tamalee
T
Ménard
Cynthia
C
Coleman
C Norman
CN
Brechbiel
Martin W
MW
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry*; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D042783:Endothelial Cells / Q000187:drug effects; D005347:Fibroblasts; D005910:Glioma; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014471:Umbilical Veins
D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D003514:Cyclohexylamines; D011725:Pyridines; C114047:tachpyr; D003300:Copper