Title:Organoselenium Compounds as Potential Neuroprotective Therapeutic Agents
Volume: 20
Issue: 2
Author(s): Waseem Hassan, Claudia S. Oliveira, Hamsa Noreen, Jean P. Kamdem, Cristina W. Nogueira and Joao B.T. Rocha
Affiliation:
Keywords:
Organochalcogens, neuroprotection and lipid peroxidation inhibition.
Abstract: Selenium plays its physiological chemistry in mammalian living cells as the selenol
group of a selenocysteinyl residue found in few numbers of selenoproteins. These proteins have
antioxidant properties and catalyze redox reactions, for instance, the selenol-mediated decomposition
of peroxides (glutathione peroxidase catalyzed reactions) or the selenol-thiol-mediated
reduction of disulfide bonds (the thioredoxin reductase catalyzed reactions). Organochalcogens
can mimic the glutathione peroxidase activity (GPx-like activity) by diverse mechanisms. Ebselen
and diphenyl diselenide are two types of organoselenium compounds that have been extensively studied in the literature because they
posses interesting biochemical and pharmacological properties. They can interact with reactive species (peroxynitrite, peroxides) and
have anti-inflammatory properties. Ebselen was used with borderline efficacy in human trials associated with brain ischemia/reperfusion.
Experimental models confirmed the neuroprotective effects of ebselen and diselenides in a variety of in vitro and in vivo models of neurotoxicity,
including those associated with brain ischemia and acidosis. Ebselen is registered as a safe drug, but it has not yet been approved
for the treatment of brain pathologies. In fact, the major problem with organoselenium compounds is that they have no specific
target, but modulate general physiological/pathological processes (e.g., inflammatory response/oxidative stress). Thus, the future of organoselenium
compounds as potential therapeutic agent will require the synthesis of target-directed molecules.
