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