Paradoxical Behavior of Organodiselenides: Pro-oxidant to Antioxidant

Over the years, organodiselenides have emerged as the biologically relevant class of molecules. On one hand, such compounds are known for pro-oxidant effects leading to toxicity in biological systems. On the other hand, there are growing evidences about their bio-mimetic activities as catalysts such as thiol-peroxidase or glutathione peroxidase (GPx)-like activity. Our recent work has explored this paradoxical behavior of diseledides in developing radioprotectors and/or anticancer agents. For this, a number of diselenides of alkyl, nicotinamide and pyridine derivatives have been evaluated in different biological models. The results have shown that diselenides exhibit not only antioxidant effect in cells against radiation damage but can also use the same mechanism to induce cell death in tumor cells [1-3]. Specifically diselenide like 2,2’-dipyridyl diselenide activates biological mechanism of cell cycle perturbation, unfolded protein response and apoptosis in lung cancer (A549) cells through reductive rather than oxidative stress and is based on a shift of the ratio of the thiol redox pairs (GSH and GSSG) on the side of reduction rather than towards oxidation. The cell free studies have indicated that diselenide acts as a substrate of thioredoxin reductase (TrxR) and accordingly it has been postulated that TrxR mediated reduction of diselenides within cells may generate intermediates leading to reductive environment. Additionally, our group has also reported that diselenide compounds can be effective inhibitor of viral proteases, a property useful in developing anti-viral drugs [4]. These finding gain a lot of significance in understanding toxicology and pharmacology of diselenides.