Synthesis of a Hybrid between SOD Mimetic and Ebselen to Target Oxidative Stress

Oxidative stress emerged as target in drug discovery due to its diverse role in various diseases, such as cardiovascular, neurodegenerative, and autoimmune diseases. During the last decades, considerable progress was made in the development of compounds with the ability to reduce reactive oxygen species (ROS) like superoxide. However, the dismutation of the latter leads to formation of another harmful ROS, hydrogen peroxide, which can be depleted through peroxidase activity. The present work describes the synthesis of a hybrid, which unifies a superoxide dismutase mimetic, Mn(II)pyane, and a glutathione peroxidase mimetic, ebselen, that are connected via an amide bond. This unique hybrid is designed in order to convert superoxide into oxygen and water, i.e. as a potential biological agent for complete ROS removal and will be used in the future as mechanistic molecular tool for further elucidation of (patho) physiological consequences of ROS removal.