Influence of substituent heteroatoms on the cytoprotective properties of pyrimidinol antioxidants

Arnaud Chevalier, Omar M. Khdour, Margaret Schmierer, Indrajit Bandyopadhyay, Sidney M. Hecht, Bioorganic & Medicinal Chemistry, Available online 23 January 2017, ISSN 0968-0896, doi:10.1016/j.bmc.2017.01.030.

Defects in mitochondrial function are linked to numerous neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Friedreich’s ataxia, and are the hallmarks of a number of genetic mitochondrial disorders whose manifestations range from muscle weakness to organ failure. In this context, improvements in mitochondrial function and cellular bioenergetics represent potential targets for therapeutic intervention in mitochondrial diseases.
These compounds are able to quench ROS and lipid peroxidation, maintain mitochondrial membrane potential and confer cytoprotection to cultured cells under conditions of induced oxidative stress. These properties are related to their ability to quench reactive oxygen radicals; therefore, the compounds have been denoted multifunctional radical quenchers (MRQs).
The ability of these compounds to quench lipid peroxidation induced by depletion of glutathione with diethyl maleate (DEM) was evaluated in Friedreich’s ataxia (FRDA) lymphocytes.


 Influence of substituent heteroatoms on the cytoprotective properties of pyrimidinol antioxidants