Towards multifunctional antioxidants: synthesis, electrochemistry, in vitro and cell culture evaluation of compounds with ligand/catalytic properties.

Numerous human diseases are linked to a biochemical condition known as oxidative stress (OS). Antioxidants are therefore becoming increasingly important as potential disease prevention and therapeutic agents. Since OS is a multi-stressor event, agents combining a range of different antioxidant properties, such as redox catalysis and metal binding, might be more effective and selective than mono-functional agents. Selenium derivatives of aniline and pyridine combine redox activity with metal binding properties. These multifunctional agents have a distinct electrochemical profile, and exhibit good catalytic activity in the glutathione peroxidase mimic and metallothionein assays. They also show antioxidant activity in a skin cell model of UVA-induced stress. These compounds might therefore provide the basis for novel agents combining two or more distinct antioxidant properties.

[1]  K. Tasker,et al.  Asymmetric organotellurides as potent antioxidants and building blocks of protein conjugates. , 2005, Organic & biomolecular chemistry.

[2]  R. Tyrrell,et al.  Susceptibility of skin cells to UVA-induced necrotic cell death reflects the intracellular level of labile iron. , 2004, The Journal of investigative dermatology.

[3]  G. Kontoghiorghes,et al.  The design and development of deferiprone (L1) and other iron chelators for clinical use: targeting methods and application prospects. , 2004, Current medicinal chemistry.

[4]  J. Rocha,et al.  Protective role of aryl and alkyl diselenides on lipid peroxidation. , 2004, Environmental research.

[5]  L. Latterini,et al.  Photophysical and Photobiological Behavior of Antimalarial Drugs in Aqueous Solutions , 2004, Photochemistry and photobiology.

[6]  L. Klotz,et al.  Evaluation of sulfur, selenium and tellurium catalysts with antioxidant potential. , 2003, Organic & biomolecular chemistry.

[7]  R. Tyrrell,et al.  Epicatechin and its methylated metabolite attenuate UVA-induced oxidative damage to human skin fibroblasts. , 2003, Free radical biology & medicine.

[8]  Claus Jacob,et al.  Sulfur and selenium: the role of oxidation state in protein structure and function. , 2003, Angewandte Chemie.

[9]  K. Bhasin,et al.  A novel and convenient synthesis towards 2-pyridylselenium compounds: X-ray crystal structure of 4,4′-dimethyl-2,2′-dipyridyl diselenide and tris(2-pyridylseleno)methane , 2002 .

[10]  C. Peers,et al.  Electrochemistry of chalcogen compounds: prediction of antioxidant activity. , 2001, Chemical communications.

[11]  M. Parnham,et al.  Ebselen: prospective therapy for cerebral ischaemia , 2000, Expert opinion on investigational drugs.

[12]  R. Tyrrell,et al.  Ultraviolet A radiation induces immediate release of iron in human primary skin fibroblasts: the role of ferritin. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Maret,et al.  Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. Maret,et al.  Ebselen, a selenium-containing redox drug, releases zinc from metallothionein. , 1998, Biochemical and biophysical research communications.

[15]  W. Maret,et al.  Control of zinc transfer between thionein, metallothionein, and zinc proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Rorabacher,et al.  Avoiding interferences from Good's buffers: A contiguous series of noncomplexing tertiary amine buffers covering the entire range of pH 3-11. , 1997, Analytical biochemistry.

[17]  Julian L. Roberts,et al.  Electrochemistry for Chemists , 1995 .

[18]  M. Iwaoka,et al.  A Model Study on the Effect of an Amino Group on the Antioxidant Activity of Glutathione Peroxidase , 1994 .

[19]  H. Sies Strategies of antioxidant defense , 1993 .

[20]  B. Halliwell Reactive oxygen species in living systems: source, biochemistry, and role in human disease. , 1991, The American journal of medicine.

[21]  J. R. Hartman,et al.  Crown thioether chemistry. Synthetic, structural, and physical studies of the copper(II) and copper(I) complexes of hexathia-18-crown-6 , 1986 .

[22]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[23]  I. Fujiwara,et al.  Improved synthesis and stability of 8-selenoquinoline and its sodium salt as organic reagents. , 1972, Talanta.

[24]  G. Cooper,et al.  Complex Ions. I. The Identification of Complex Ions in Solution by Spectrophotometric Measurements , 1941 .

[25]  M. Vitek,et al.  Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical. , 2004, Free radical biology & medicine.

[26]  M. Vašák Standard isolation procedure for metallothionein. , 1991, Methods in enzymology.