Targeting selenium metabolism and selenoproteins: novel avenues for drug discovery.
Selenoproteins play a wide range of roles in metabolism and oxidative stress defense and are produced by organisms in all three domains of life. Recent evidence has been presented that metal based cancer drugs target the selenol nucleophile of the active site selenocysteine in thioredoxin reductase isoenzymes. Other metals and metalloids, such as tin, arsenic and gold, have also recently been shown to form stable complexes with hydrogen selenide, a required precursor for the synthesis of selenoproteins in all biological organisms. Moreover these metal based compounds have been shown to inhibit growth of pathogens such as Clostridium difficile and Treponema denticola due to their reactivity with this highly reactive metabolic precursor. This review summarizes the recent finding on these two avenues for drug discovery, and puts this work in context with the larger field of selenium biology.
Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, FL, USA. wself@mail.ucf.edu.
Sarah Elizabeth
SE
Jackson-Rosario
William Thomas
WT
Self
D000818:Animals; D003141:Communicable Diseases / Q000188:drug therapy; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000378:metabolism*
D051140:Selenoproteins; D012643:Selenium