Selenium-based drug design: rationale and therapeutic potential

The wide media coverage given recently to a study correlating higher selenium levels with a reduced risk of advanced prostate cancer is but the latest addition to a growing body of epidemiological findings which link dietary selenium deficiency to diseases as diverse as cancer, heart disease, arthritis and AIDS. Indeed, selenium has a long history of association with human health and disease. Moreover, direct evidence is now emerging for specific beneficial effects of dietary selenium supplementation. Thus, the pharmacology, biology and biochemistry of selenium metabolism have become subjects of intense current interest. At the molecular level, selenium (as selenocysteine) is an essential component of the active sites of the enzymes glutathione peroxidase, iodothyronine 5'-deiodinase and mammalian thioredoxin reductase, and is also present in several other mammalian selenoproteins. Both glutathione peroxidase and thioredoxin reductase catalyse reactions essential to the protection of cellular components against oxidative and free radical damage. As a consequence of the growing recognition of the important biological role of selenium, a number of novel pharmaceutical agents, either selenium-based or which target specific aspects of selenium metabolism, are under development. Among these are orally active selenium-based antihypertensive agents, anticancer, antiviral, immunosuppressive and antimicrobial agents, and organoselenium compounds which reduce oxidative tissue damage and oedema. It can be anticipated that as our understanding of the basic biology and biochemistry of selenium increases, future efforts will uncover even more sophisticated approaches for the rational development of new selenium-based pharmaceutical agents.