Diselenide Derivative, Potential Successor of Ebselen with High Antioxidant Activity: Assessment on in vitro Models

Oxidative stress plays a key role in several pathophysiological events, including the attack of DNA, cell membrane damage and signaling pathways disruption. The harmful effect of oxidant stress has been attributed to a high production of reactive oxygen species (ROS) followed by a depletion of antioxidant enzymes, glutathione peroxidase (GPx), a mammalian selenoenzyme which functions as a catalytic antioxidant, has been described to protect various organisms against oxidative stress. In the past two decades, the design of small weight molecules such as ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), has renewed the interest of synthetic analogues able to mimic the GPx activity. From four in vitro in vitro models, we previously showed that ebselen and some of its analogues (compounds 1, 2, 3 and 4) not only behaved at various degrees as GPx-like mimics but also as antioxidants especially for diselenide derivative (3). The present study deals with the antioxidant effect of diselenide derivative (3) versus ebselen on cellular model and the enzyme myeloperoxidase (MPO) activity using the in vitro systems. Derivative (3) has been chosen because of its interesting antioxidant profile in cell-free systems.