title: Synthesis, characterization, and cytotoxicity studies of Cu(II), Zn(II), and Fe(III) complexes of N-derivatized 3-hydroxy-4-pyridiones.
abstract: The deleterious role of metal ions in Alzheimer's disease has inspired the study of various metal chelators. We previously showed the synthesis and in vitro activity of several bidentate hydroxypyridinone compounds, including 3-hydroxy-2-methyl-1-phenyl-4(1H)-pyridinone (1), 1-(4-aminophenyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (2), and 1-(2-benzothiazolyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (3). While the focus has been on the Cu(II) ion, the other biorelevant metals, Zn(II) and Fe(III) have been largely neglected. Herein, we report the synthesis of Zn(II) and Fe(III) complexes of ligands 1, 2, and 3, and their characterization by infrared (IR) spectroscopy, high resolution mass spectrometry (HR-MS), elemental analysis, and NMR, where applicable. Solid state structures of Zn(1)2, Fe(1)3, and Cu(3)2 are analyzed with X-ray crystallography. The cytotoxicity of pro-ligands 1, 2, and 3, and the three metal complexes of 2 are examined in a neuronal cell line to determine the effect of metal chelation on toxicity of the compounds.
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Telpoukhovskaia
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Rodríguez
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Scott
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
authors.forename: Brent D G
authors.initials: BD
authors.lastname: Page
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Patrick
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. Electronic address: orvig@chem.ubc.ca.
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002614:Chelating Agents / Q000737:chemistry / Q000633:toxicity; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects; D009584:Nitrogen / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry* / Q000633:toxicity*; D015032:Zinc / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D008024:Ligands; D011728:Pyridones; D003300:Copper; D007501:Iron; D015032:Zinc; D009584:Nitrogen
keywords: Alzheimer's disease; Copper; Hydroxypyridinone; Iron; Metal complex cytotoxicity; Zinc