Theoretical insights into the antiradical activity and copper-catalysed oxidative damage of mexidol in the physiological environment

Mexidol (MD, 2-ethyl-6-methyl-3-hydroxypyridine) is a registered therapeutic agent for the treatment of anxiety disorders. The chemical structure suggests that MD may also act as an antioxidant. In this study, the hydroperoxyl radical scavenging activity of MD was studied to establish baseline antioxidant activity, followed by an investigation of the effect of MD on the copper-catalysed oxidative damage in biological systems, using computational methods. It was found that MD exhibits moderate radical scavenging activity against HOO(•) in water and pentyl ethanoate solvents following the single electron transfer and formal hydrogen transfer mechanisms, respectively. MD can chelate Cu(II), forming complexes that are much harder to reduce than free Cu(II): MD chelation completely quenches the Cu(II) reduction by ascorbic acid and suppresses the rate of reduction reaction by [Formula: see text] that are the main reductants of Cu(II) in biological environments. Therefore, MD exerts its anti-HO(•) activity primarily as an OIL-1 inhibitor.