Electron-deficient ortho Mn(III) N-substituted pyridylporphyrins (MnPs) are promising therapeutics for diseases where cellular redox status (ratio of endogenous reactive species and antioxidants) is perturbed. These compounds were developed based on: (1) redox property of Mn site; (2) ability to eliminate superoxide as efficiently as superoxide dismutase (SOD) enzymes; and (3) efficacy in protecting SOD-deficient E. coli and S. cerevisiae. Their SOD-like potency parallels their efficacy in reducing peroxynitrite and several other reactive species, as well as reactivity towards signaling protein cysteines. Such actions, dominated by electron-deficiency of Mn site, translate into redox modulation of cellular transcriptional activity, and in turn leads to suppression of inflammatory and immune disorders. The core N-pyridylporphyrin structure was further modified to increase MnP mitochondrial accumulation and transport across blood-brain barrier. Remarkable efficacy of MnPs in cancer, radiation injury, diabetes and central nervous system disorders, along with most recent optimization efforts, drives MnPs aggressive clinical development.

Structure-activity and bioavailability studies drive development of cationic Mn porphyrins as cancer and central nervous system therapeutics

244th National Meeting (2012)

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