title: Evaluation of copper chelation agents as anti-angiogenic therapy.
abstract: 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.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room B3B69, Bethesda, MD 20892-1002, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Mary
authors.initials: M
authors.lastname: Sproull
authors.forename: Steve
authors.initials: S
authors.lastname: Tantama
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sankineni
authors.forename: Tamalee
authors.initials: T
authors.lastname: Scott
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
authors.forename: C Norman
authors.initials: CN
authors.lastname: Coleman
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: 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
chemical_list: D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D003514:Cyclohexylamines; D011725:Pyridines; C114047:tachpyr; D003300:Copper