The Design of Multifunctional Antioxidants Against the Damaging Ingredients of Oxidative Stress

Abstract

Oxidative stress is a biochemical condition associated with a sharp increase in intracellular concentrations of a range of oxidative stressors, including reactive oxygen species, reactive nitrogen species and labile metal ions. It is associated with a wide range of human disorders, such as inflammatory diseases, neurodegenerative diseases, glaucoma, and cancer. Equally importantly, oxidative stress is pronounced in older people, which makes it an important matter in an ageing Society. Not surprisingly, antioxidants have become a major focus of modern drug development. While natural antioxidants, such as phenolic aromatic compounds, vitamin C, vitamin E and curcumin have shown promising results, the development of effective synthetic antioxidants is often problematic. We have recently proposed the rational design of multifunctional antioxidants which target oxidative stressors in a more comprehensive manner. Such compounds may, for instance, combine catalytic sites with metal binding sites. Here we present the synthesis of representative molecules with combined catalytic and metal binding properties. The apparent ‘antioxidant’ activities have been studied in vitro and, for the most promising compound, have been confirmed in cultured skin cells exposed to UVA radiation.

Keywords:

• Antioxidants
• catalysis
• metal binding
• radiation damage
• selenium

Acknowledgments

The authors are indebted to the following colleagues in the UK and Germany for their tireless support and advice with synthesis, electrochemistry, complex chemistry and, of course, working with FEK4 and FCP7 cells: Rex Tyrrell (University of Bath), Jennifer Littlechild (University of Exeter), James Tucker (University of Birmingham), Kaspar Hegetschweiler (Saarland University) and Awais Anwar (Saarland University).

The authors would also like to acknowledge financial support from Saarland University, the Ministry of Culture of the Saarland, Fresenius Medical Care (stipend T.B.), DAART (UK) (stipend for C.A.C.), EATL (for F.H.F.) and the University of Exeter. This financial support has not caused any conflict of interest to any of the participating authors.