Selenium-based drug design

Abstract

The biochemistry, pharmacology and epidemiology of selenium and selenium-containing compounds continue to be subjects of considerable interest from the viewpoint of public health. Selenium has a long history of association with human health and disease, and we now recognize that this element is an essential nutrient that is critical to key cellular processes. We now know that the selenoproteins constituting the human selenoproteome are encoded by 25 genes in the human genome, and much progress is being made in our understanding of selenium metabolism and the health effects of selenium metabolites in normal and disease states. The idea that selenium-containing dietary supplements might be effective in preventing disease has gone through both optimistic and pessimistic phases in recent years, and the future prospects for such a nutritional approach are unclear at the present time. In contrast, a significant number of promising efforts are underway that are aimed at designing and developing pharmaceutical agents that are selenium-based or that target specific aspects of selenium metabolism. This chapter focuses on some of these efforts to develop new selenium-based anticancer, antioxidant, antihypertensive, antiviral, immunosuppressive, and antimicrobial agents. While most of the efforts that entail designed organoselenium compounds – as opposed to inorganic selenium metabolites – are still at the preclinical stage, evidence is emerging that selenium-based compounds can operate via several beneficial biochemical and pharmacological mechanisms. Since our understanding of the biology, biochemistry and pharmacology of selenium and selenoproteins is rapidly expanding, we can anticipate that the coming years will bring further development of new selenium-based pharmaceutical agents with therapeutic potential against human diseases.