Salen Mn Complexes are Superoxide Dismutase/Catalase Mimetics that Protect the Mitochondria

Salen Mn complexes, including EUK-134, EUK-189 and a cyclized analog EUK-207, are synthetic superoxide dismutase (SOD) and catalase mimetics that are beneficial in many models of oxidative stress. Though not designed to target the mitochondria, salen Mn complexes show "mito-protective" activity, that is, an ability to attenuate mitochondrial injury, in various experimental systems. Treatment with EUK-134 prevents respiratory chain abnormalities induced by ionizing radiation in rat astrocyte cultures. Treatment with salen Mn complexes also prolongs survival, protects mitochondrial enzymes and prevents oxidative pathologies in Sod2-/mice, which lack the mitochondrial form of superoxide dismutase. Recently, EUK-207 was shown to attenuate ischemia reperfusion injury, including mitochondrial dysfunction, in hearts from ABC-me-/+ mice, which are deficient in a mitochondrial transporter and more vulnerable to oxidative stress. Since mitochondrial dysfunction has been implicated in many forms of injury and degeneration, this "mito-protective" property may explain some of the cytoprotective effects of salen Mn complexes in vivo, and may also enhance their potential therapeutic value.