title: Dinuclear copper(II) complexes with valsartan. Synthesis, characterization and cytotoxicity.
abstract: Two novel dinuclear complexes involving the antihypertensive drug valsartan and copper(II) ion have been prepared in water and DMSO. The complex compositions were determined as: [Cu(vals)(H(2)O)(3)](2).6H(2)O and [Cu(vals)(H(2)O)(2)DMSO](2).2H(2)O. They were thoroughly characterized by elemental and thermal analysis, spectrophotometric titrations and UV-visible, diffuse reflectance, FTIR, Raman and EPR spectroscopies. No effect of the ligand on two tested osteoblastic cell lines in culture (one normal MC3T3E1 and one tumoral UMR106) was observed in concentrations up to 100 μM. Higher concentrations of Valsartan are required to induce cytotoxicity in both cell lines. The antiproliferative effect of the tested complex ([Cu(vals)(H(2)O)(3)](2).6H(2)O) in a dose-response manner, was higher in the UMR106 osteoblastic cell line than that of the MC3T3E1 normal line at concentrations ≥100 μM. Morphological alterations are in accordance with proliferative observations.
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, UNLP, 47 y 115 (1900) La Plata, Argentina.
authors.forename: Susana B
authors.initials: SB
authors.lastname: Etcheverry
authors.forename: Ana L
authors.initials: AL
authors.lastname: Di Virgilio
authors.forename: Otaciro R
authors.initials: OR
authors.lastname: Nascimento
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013777:Tetrazoles / Q000737:chemistry* / Q000494:pharmacology; D013818:Thermogravimetry; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D013777:Tetrazoles; D003300:Copper; D000068756:Valsartan; D014633:Valine