ORIGINAL PAPER Orally available Mn porphyrins with superoxide dismutase and catalase activities

The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen spe-cies, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are pro-tective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismu-tase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series com-pounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral ther-apeutic agents for cellular damage caused by oxidative stress