| 12818794 |
Kachadourian R, Flaherty MM, Crumbliss AL, Patel M, Day BJ: Synthesis and in vitro antioxidant properties of manganese (III) beta-octabromo-meso-tetrakis (4-carboxyphenyl) porphyrin. J Inorg Biochem. 2003 Jul 1;95(4):240-8.
Manganese (III) meso-tetrakis (4-carboxypheny) porphyrin (MnTBAP) is a readily available and widely used agent to scavenge reactive oxygen species. A major limitation of MnTBAP is its relatively weak potency due to its low metal centered redox potential. The goal of these studies was to prepare a more potent analog of MnTBAP by increasing its redox potential through beta-substitution on the porphyrin ring by bromination. Manganese (III) beta-octabromo-meso-tetrakis (4-carboxyphenyl) porphyrin (MnBr (8) TBAP) was prepared in three steps starting from the methyl ester of the free ligand meso-tetrakis (4-carboxyphenyl) porphyrin, with an overall yield of 50%. The superoxide dismutase (SOD)-like activity of MnBr (8) TBAP (IC (50)=0.7 microM) was the same as manganese (III) meso-tetrakis (N-methylpyridinium-4-yl) porphyrin (MnTM-4-PyP (5+)), while the metal-centered redox potential of the first was considerably higher than the second (E (1/2)=+128 and 0 mV vs. normal hydrogen electrode, respectively). However, a number of these cationic Mn-porphyrins (such as MnTM-4-PyP (5+)) redox-cycle with cytochrome P450 reductase in the presence of oxygen and NADPH whereas MnTBAP and its halogenated analog, MnBr (8) TBAP do not. The enhanced ability of MnBr (8) TBAP to inhibit paraquat- and hypoxia-induced injuries in vitro is also reported. In these in vitro models, in which cationic Mn-porphyrins exhibit very low activity, MnBr (8) TBAP appears to be at least eightfold more active than the non-brominated analog MnTBAP. |
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