Developing ROS scavenging agents for pharmacological purposes: Recent advances in design of manganese-based complexes with anti-inflammatory and anti-nociceptive activity

Current Medicinal Chemistry

Volumn 19, Issue 26, 2012, Pages 4431-4444

  Bani, D ^a   Bencini, A ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

Author keywords

Anti inflammatory ability; Antioxidants; Corroles; Free radicals; Macrocycles; Manganese complexes; Polyamine polycarboxylic acids; Polyamines; Porphyrins; RNS scavengers; ROS scavengers; Salen derivatives; SOD mimetics

Indexed keywords

HYDROGEN PEROXIDE; IMISOPASEM MANGANESE; MANGANESE DERIVATIVE; PEROXYNITRITE; REACTIVE OXYGEN METABOLITE; SC 72325; SUPEROXIDE; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINOCICEPTION; ARTICLE; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG SAFETY; DRUG STABILITY; DRUG TARGETING; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; THERMODYNAMICS;

ANALGESICS; ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; COORDINATION COMPLEXES; DRUG DESIGN; FREE RADICAL SCAVENGERS; HUMANS; MANGANESE; REACTIVE OXYGEN SPECIES;

EID: 84868022361     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712803251476     Document Type: Article

References (109)

1. Winterbourn, C.C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol, 2008, 4(5), 278-286.
2. Finkel, T. Signal transduction by reactive oxygen species. J. Cell. Biol., 2011, 194(1), 7-15.
3. Finkel, T. Radical medicine: treating ageing to cure disease. Nat. Rev. Mol. Cell. Biol, 2005, 6(12), 971-976.
4. Salvemini, D.; Little, J.W.; Doyle, T.; Neumann, W.L. Roles of reactive oxygen and nitrogen species in pain. Free Radic. Biol. Med., 2011, 51(5), 951-966.
5. Kvietys, P.R.; Granger, D.N. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic. Biol. Med., 2012, 52(3), 556-592.
6. Fridovich, I. Superoxide dismutases. An adaptation to a paramagnetic gas. J. Biol. Chem., 1989,264(14), 7761-7764.
7. Johnson, F.; Giulivi, C. Superoxide dismutases and their impact upon human health. Mol. Aspects Med., 2005, 26(4-5), 340-352.
8. Wang, Z.Q.; Porreca, F.; Cuzzocrea, S.; Galen, K.; Lightfoot, R; Masini, E.; Muscoli, C; Mollace, V.; Ndengele, M.; Ischiropoulos, H.; Salvemini, D. A newly identified role for superoxide in inflammatory pain. J. Pharmacol Exp. Ther., 2004, 309(3), 869-878.
9. Reddy, J.K.; Rao, M.S. Oxidative DNA damage caused by persistent peroxisome proliferation: its role in hepatocarcinogenesis. Mutat. Res., 1989, 214(1), 63-68.
10. Mittal, C.K.; Murad, F. Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'- monophosphate formation. Proc. Natl. Acad. Sci. USA, 1977, 74(10), 4360-4364.
11. Salvemini, D; Riley, D.P. Nonpeptidyl mimetics of superoxide dismutase in clinical therapies for diseases. Cell Mol Life Sci., 2000, 57(11), 1489-1492.
12. Muscoli, C; Cuzzocrea, S.; Riley, D.P.; Zweier, J.L.; Thiemermann, C; Wang, Z.Q.; Salvemini, D. On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies. Br. J. Pharmacol, 2003, 140(3), 445-460.
13. Petkau, A. Scientific basis for the clinical use of superoxide dismutase. Cancer Treat. Rev., 1986, 13(1), 17-44.
14. McCord, J.M.; Edeas, M.A. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed. Pharmacother., 2005, 59(5), 139-142.
15. Slemmer, J.E.; Shacka, J.J.; Sweeney, M.I.; Weber, J.T. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr. Med. Chem.,2008,15(4), 404-414.
16. Riley, D.P.; Weiss, RH. Manganese macrocyclic ligand complexes as mimics of superoxide dismutase. J. Am. Chem. Soc, 1994, 116(1), 387-388.
17. Riley, D.P. Functional mimics of superoxide dismutase enzymes as therapeutic agents. Chem. Rev., 1999, 99(9), 2573-2588.
18. Zhang, C.X.; Lippard, S.J. New metal complexes as potential therapeutics. Curr. Opin. Chem. Biol, 2003, 7(4), 481-489.
19. Cuzzocrea, S; Thiemermann, C; Salvemini, D. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr. Med. Chem., 2004, 11(9), 1147-1162.
20. Riley, D.P.; Schall, O.F. Structure-activity studies and the design of synthetic superoxide dismutase (SOD) mimetics as therapeutics. Adv. Inorg. Chem., 2006, 59(1), 233-263.
21. Batinic-Haberle, I., Rajic, Z., Tovmasyan, A., Reboucas, J.S., Ye, X., Leong, K.W., Dewhirst, M.W., Vujaskovic, Z., Benov, L., Spasojevic, I. Diverse functions of cationic Mn(III) N-substituted pyridylporphyrins, recognized as SOD mimics. Free Radic. Biol Med., 2011, 51(5), 1035-1053.
22. Batinic-Haberle, I; Spasojevic, I.; Hambright. P.; Benov, L.; Crumbliss, A. L.; Fridovich, I. Relationship between redox potential, proton dissocation contsnts of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activies of manganese(III) and iron(III) water-soluble porphyrins. Inorg. Chem., 1999, 38(18), 4011-4022.
23. Wolak, M.; van Eldik, R Mechanistic studies on peroxide activation by a water-soluble iron(III)-porphyrin: implications for O-O bond activation in aqueous and nonaqueous solvents. Chem. Eur. J., 2007, 13(17), 4873-4883.
24. Baker, K.; Bucay Marcus, C; Kruk, H.; Malfroy, B.; Doctrow, S.R. Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stoke model: a key role for a reactive oxygen species in ischemic brain injury. J. Pharmacol. Exp. Ther., 1998, 284(1), 215-221.
25. Salvemini, D.; Wang, Z.Q.; Zweier, J.L.; Samouilov, A; Macarthur, H.; Misko, T.P.; Currie, M.G.; Cuzzocrea, S.; Sikorski, J.A.; Riley, D.P. A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science, 1999, 286(5438), 304-306.
26. Salvemini, D.; Riley, D.P.; Cuzzocrea, S. SOD mimetics are coming of age. Nature Rev. Drug Discov., 2002, 1(5), 367-374.
27. Sheng, H.; Enghild, J.J.; Bowler, R; Pate, M.; Batinic-Haberle, I.; Calvi, C.L.; Day, B.J.; Pearlstein, R D.; Crapo, J.D.; Warner, D. S. Effect of metalloporphyrin catalytic antioxidants in experimental brain ischemia Free Radic. Biol. Med., 2002, 33(7), 947-961.
28. Batinic-Haberle, I.; Reboucas, J.S.; Spasojevic, I. Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antiox. Redox Signal., 2010, 13(6), 877-918.
29. Miriyala, S., Spasojevic, I., Tovmasyan, A., Salvemini, D., Vujaskovic, Z., St Clair, D., Batinic-Haberle, I. Manganese superoxide dismutase, MnSOD and its mimics. Biochim. Biophys. Acta, 2012, 1822(5), 794-814.
30. Bencini, A.; Failli, P.; Valtancoli, B.; Bani, D. Low molecular weight compounds with transition metals as free radical scavengers and novel therapeutic agents. Cardiovasc. Hematol. Agents Med. Chem., 2010, 8(3), 128-146.
31. Riley, D.P.; Lennon, P.J.; Neumann, W.L.; Weiss, R.H. Toward the rational design of superoxide dismutase mimics: mechanistic studies for the elucidation of substituent effects on the catalytic activity of macrocyclic manganese(II) complexes. J. Am. Chem. Soc, 1997, 119(28), 6522-6528.
32. Riley, D.P.; Henke, S.L.; Lennon, P.L.; Weiss, R.H.; Neumann, W.L.; Rivers, W.J. Jr.; Aston, K.W.; Sample, K.R.; Rahman, H.; Ling, C.S.; Shieh, J.J.J.; Busch, D.H.; Szulbinski, W. Synthesis, characterization, and stability of manganese(II) C-substituted 1,4,7,10,13-pentaazacyclopentadecane complexes exhibiting superoxide dismutase activity. Inorg. Chem., 1996, 35(18), 5213-5231.
33. Riley, D.P. Rational design of synthetic enzymes and their potential utility as human pharmaceuticals: development of manganese(II)-based superoxide dismutase mimics. Adv. Supramol. Chem., 2000, 6(1), 217-242.
34. Aston, K.V.; Rath, N.; Naik, A.; Slomczynska, U.; Schall, O.F.; Riley, D.P Computer-aided design (CAD) of Mn(II) complexes: superoxide dismutase mimetics with catalytic activity exceeding the native enzyme. Inorg. Chem., 2001,40(8), 1779-1789.
35. Dees, A.; Zahl, A.; Puchta, R.; van Eikema Hommes, N.J.R.; Heinemann, F. W.; Ivanovic-Burmazovic, I. Water exchange on seven-coordinate Mn(II) complexes with macrocyclic pentadentate ligands: insight in the mechanism of Mn(II) SOD mimetics. Inorg. Chem., 2007, 46(7), 2459-2470.
36. Ivanovic-Burmazovic, I. Catalytic dismutation vs. reversible binding of superoxide. Adv. Inorg. Chem., 2008, 60(1), 59-100.
37. Cuzzocrea, S.; Riley, D.P.; Caputi, A.P.; Salvemini, D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol. Rev., 2001, 53(1), 135-159.
38. Salvemini, D., Cuzzocrea, S. Superoxide, superoxide dismutase and ischemic injury. Curr. Opin. Investig. Drugs, 2002, 3(6), 886-895.
39. Salvemini, D.; Neumann, W. Targeting peroxynitrite driven nitroxidative stress with synzymes: A novel therapeutic approach in chronic pain management. Life Sci., 2010, 86(15-16), 604-614.
40. Cotton, F.A.; Wilkinson, G. Advanced Inorganic Chemistry. 1998 John Wiley & Sons, NY.
41. Schmidt, C.K.; Brauch, H.J. Impact of aminopolycarboxylates on aquatic organisms and eutrophication: overview of available data. Environ. Toxicol., 2004, 19(6), 620-637.
42. Fricker, S.P. Metal complexes as therapeutic agents in nitrogen monoxide modulation. In: Metal ions in biological systems; Vol 41. Sigel, A.; Sigel, H. Eds.; Marcel Dekker: NY, 2004; pp. 421-80.
43. Failli, P.; Bani, D.; Bencini, A.; Cantore, M.; Di Cesare Mannelli, L.; Ghelardini, C; Giorgi, C; Innocenti, M.; Rugi, F.; Spepi, A.; Udisti, R.; Valtancoli, B. A novel manganese complex effective as superoxide anion scavenger and therapeutic agent against cell and tissue oxidative injury. J. Med. Chem., 2009, 52(22), 7273-7283.
44. Bencini, A.; Bianchi, A.; Micheloni, M.; Paoletti, P.; Garcia-España, E.; Niño, M.A. Co-ordination tendency of [3k]aneNk polyazacycloalkanes. Thermodynamic study of solution equilibria. J. Chem. Soc. Dalton Trans., 1991,5(1), 1171-1174.
45. 2DO2A), a novel superoxide scavenger compound. Free Radic. Biol. Med., 2010, 48(11), 1525-1534
46. Bruce, A.J.; Malfroy, B.; Baudry, M. β-Amyloid toxicity in organotypic hippocampal cultures: Protection by EUK-8, a synthetic catalytic free radical scavenger. Proc. Natl. Acad. Sci. (USA), 1996, 93(6), 2312-2316.
47. Malfroy, B.; Doctrow, S.R.; Orr, P.L.; Tocco, G.; Fedoseyeva, E.V; Benichou, G. Prevention and suppression of autoimmune encephalomyelitis by EUK-8,a synthetic catalytic scavenger of oxygen reactive metabolites. Cell. Immunol, 1997, 177(1), 62-68.
48. Doctrow, S.R.; Baudry, M.; Huffman, K.; Malfroy, B.; Melov, S. In: Medicinal Inorganic Chemistry; Sessler, J.L.; Doctrow, S.R.; McMurry, T.J.; Lippard, S. J., eds. ACS Symposium Series, 2005, vol 903(18), pp.319-347.
49. Doctrow, S.R.: Huffman, K.; Marcus, C.B.; Tosco, G.; Malfroy, E.; Adinolfi, C.A.: Kruk, H.; Baker, K.; Lazarowych, N.; Mascarenhas, J.; Malfroy, B. Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies. J. Med. Chem., 2002, 45(20), 4549-4558.
50. Doctrow, S.R.; Huffman, K.; Marcus, C.B.; Musleh, W.; Bruce, A.; Baudry, M.; Malfroy, B. Salen-manganese complexes: combined superoxide dismutase/catalase mimics with broad pharmacological efficacy. Adv. Pharmacol, 1997, 38(1), 247-269.
51. Sharpe, M.A.; Ollosson, R.; Stewart, V.C.; Clark, J.B. Oxidation of nitric oxide by oxomanganese-salen complexes: A new mechanism for cellular protection by superoxide dismutase/catalase mimetics. Biochem. J., 2002, 366(1), 97-107.
52. Baker, K.; Bucay-Marcus, C; Huffman, C; Kruk, H.; Malfroy, B.; Doctrow, S.R. Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: A key role for reactive oxygen species in ischemic brain injury. J. Pharmacol. Exp. Ther, 1998, 284(1), 215-221
53. Rong, Y; Doctrow, S.R.; Tocco, G.; Baudry, M. A synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology. Proc. Natl. Acad. Sci. (USA), 1999, 96(17), 9897-9902
54. Liu, R.; Liu, I.Y; Bi, X.; Thompson, R.F.; Doctrow, S.R.; Malfroy, B.; Baudry, M. Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc. Natl Acad. Sci. (USA), 2003, 100(14), 8526-8531.
55. Ophoven, S.J.; Bauer, G. Salen-manganese complexes: sophisticated tools for the analysis of intercellular ROS signaling pathways. Anticancer Res., 2010, 30(10), 3967-3980
56. Melov, S.; Doctrow, S.R.; Schneider, J.A.; Haberson, J.; Patel, M.; Coskun, P.E.; Huffman, K.; Wallace, D.C.; Malfroy, B. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J. Neurosci., 2001, 21(21), 8348-8353.
57. Brazier, M.W.; Doctrow, S.R.; Masters, C.L.; Collins, S.J. A manganesesuperoxide dismutase/catalase mimetic extends survival in a mouse model of human prion disease. Free Radic. Biol. Med., 2008, 45(2), 184-192.
58. Gonzalez, P.K.; Zhuang, J.; Doctrow, S.R.; Malfroy, B.; Benson, P.F.; Menconi, M.J.; Fink, M.P. Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. Shock, 1996, 6 (Suppl 1), S23-S26.
59. van Empel, V.P.; Bertrand, A.T.; van Oort, R.J.; van der Nagel, R.; Engelen, M.; van Rijen, H.V; Doevendans, P.A.; Crijns, H.J.; Ackerman, S.L.; Sluiter, W.; De Windt, L.J. EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overloadinduced heart failure in the harlequin mouse mutant. J. Am. Coll. Cardiol, 2006, 48(4), 824-832.
60. Srinivasan, V; Doctrow, S.; Singh, V.K.; Whitnall, M.H. Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure. Immunopharmacol Immunotoxicol, 2008, 30(2), 271-290.
61. Rosenthal, R.A.; Fish, B.; Hill, R.P.; Huffman, K.D.; Lazarova, Z.; Mahmood, J.; Medhora, M.; Molthen, R.; Moulder, J.E.; Sonis, S.T.; Tofilon, P.J.; Doctrow, S.R. Salen Mn complexes mitigate radiation injury in normal tissues. Anticancer Agents Med. Chem., 2011, 11(4), 359-372.
62. Day, B.J. Antioxidants as potential therapeutics for lung fibrosis. Antiox. Redox Signal, 2008, 10(2), 355-370.
63. Pasternack, R.F.; Skowronek, W.R. Catalysis of the disproportionation of superoxide by metalloporphyrins. J. Inorg. Biochem., 1979, 11(3), 261-267.
64. Day, B.J.; Fridovich, I.; Crapo, J.D. Manganic porphyrins possess catalase activity and protect endothelial cells against hydrogen peroxide-mediated injury. Arch. Biochem. Biophys., 1997, 347(2), 256-262.
65. Szabo, C; Day, B.J.; Salzman, A.L. Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages using a manganese mesoporphyrin superoxide dismutase mimetic and peroxynitrite scavenger. Fed. Eur Biochem. Soc. Lett., 1996, 381(1-2), 82-86.
66. Day, B.J.; Batinic-Haberle I.; Crapo, J.D. Metalloporphyrins are potent inhibitors of lipid peroxidation. Free Radic. Biol. Med., 1999, 26(5-6), 730-736.
67. - dismutation. Mn(III) methoxyethylpyridyl- and methoxyethyli-midazolylporphyrins. J. Chem. Soc. Dalton Trans., 2004, 1696-1702.
68. Kachadourian, R.; Johnson, C.A.; Min, E.; Spasojevic, I.; Day, B.J. Flavin-dependent antioxidant properties of a new series of meso-N, N'-dialkylimidazolium substituted manganese(III) porphyrins. Biochem. Pharmacol, 2004, 67(1), 77-85.
69. Reboucas, J.S.; Spasojevic, I.; Tjahjono, D.H.; Richaud, A.; Mendez, F.; Benov, L.; Batinic-Haberle, I. Redox modulation of oxidative stress by Mn porphyrin-based therapeutics: the effect of charge distribution. Dalton Trans., 2008, 1233-1242.
70. •- dismutation by superoxide dismutase mimics. J. Biol. Chem., 2003, 278(9), 6831-6837.
71. •- dismutation. J. Chem. Soc. Dalton Trans., 2002, 2689-2696.
72. Kos, I.; Reboucas, J.S.; DeFreitas-Silva, G.; Salvemini, D.; Vujaskovic, Z.; Dewhirst, M.W.; Spasojevic, I.; Batinic-Haberle, I. Lipophilicity of potent porphyrin-based antioxidants: comparison of ortho and meta isomers of Mn(III) N-alkylpyridylporphyrins, Free Radic. Biol. Med., 2009, 47(1), 72-78.
73. Sheng, H.; Yang, W.; Fukuda, S.; Tse, H.M.; Paschen, W.; Johnson, K.; Batinic-Haberle, I.; Crapo, J.D.; Pearlstein, R.D.; Piganelli, J.; Warner, D.S. Long-term neuro-protection from a potent redox-modulating metalloporphyrin in the rat. Free Radic. Biol. Med., 2009, 47(7), 917-923.
74. Sheng, H.; Spasojevic, I.; Tse, H.M.; Jung, J.Y.; Hong, J.; Zhang, Z.; Piganelli, J.D.; Batinic-Haberle, I.; Warner, D.S. Neuroprotective efficacy from a lipophilic redox-modulating Mn(III) N-hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke and subarachnoid hemorrhage. J. Pharmacol. Exp. Ther., 2011, 338(3), 906-916.
75. Gauter-Fleckenstein, B.; Fleckenstein, K.; Owzar, K.; Jiang, C; Batinic-Haberle, I.; Vujaskovic, Z.; Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection. Free Radic. Biol. Med., 2008, 44(6), 982-989.
76. Tovmasyan, A.G.; Rajic, Z.; Spasojevic, I.; Reboucas, J.S.; Chen, X.; Salvemini, D.; Sheng, H.; Warner, D.S.; Benov, L.; Batinic-Haberle, I. Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(III) Nmethoxyalkylpyridylporphyrins, Dalton Trans., 2011, 4111-4121.
77. Lee, J. H.; Julianne, A.; Groves, J. T. Manganese Porphyrins as Redox-Coupled Peroxynitrite Reductases. J. Am. Chem. Soc. 1998, 120(30), 6053-6061.
78. Batinic-Haberle, I.; Spasojevic, I.; Fridovich, I. Tetrahydrobiopterin rapidly reduces the SOD mimic Mn(III) orthotetrakis(N-ethylpyridinium-2-yl) porphyrin. Free Radic. Biol. Med., 2004, 37(3), 367-374.
79. Ferrer-Sueta, G.; Hannibal, L.; Batinic-Haberle, I.; Radi, R. Reduction of manganese porphyrins by flavoenzymes and submitochondrial particles: A catalytic cycle for the reduction of peroxynitrite. Free Radic. Biol. Med., 2006, 41(3), 503-512.
80. Ferrer-Sueta, G.; Batinic-Haberle, I.; Spasojevic, I.; Fridovich, I.; Radi, R. Catalytic scavenging of peroxynitrite by isomeric Mn(III) Nmethylpyridylporphyrins in the presence of reductants. Chem. Res. Toxicol., 1999, 12(5), 442-449.
81. Batinic-Haberle, I.; Cuzzocrea, S.; Rebouças, J.S.; Ferrer-Sueta, G.; Mazzon, E.; Di Paola, R.; Radi, R.; Spasojevic, I; Benov, L.; Salvemini, D. Pure MnTBAP selectively scavenges peroxynitrite over superoxide: Comparison of pure and commercial MnTBAP samples to MnTE-2-PyP in two models of oxidative stress injury, an SOD-specific Escherichia coli model and carrageenan-induced pleurisy. Free Radic. Biol. Med., 2009, 46(2), 192-201.
82. Rausaria, S.; Ghaffari, M.M.; Kamadulski, A.; Rodgers, K.; Bryant, L.; Chen, Z.; Doyle, T.; Shaw, M.J.; Salvemini, D.; Neumann, W.L. Retooling Manganese(III) porphyrin-based peroxynitrite decomposition catalysts for selectivity and oral activity: a potential new strategy for treating chronic pain. J. Med. Chem., 2011, 54(24), 8658-8669.
83. Day, B.J. Catalase and glutathione peroxidase mimics. Biochem. Pharmacol., 2009, 77(3), 285-296.
84. Szabo, C; Day, B.J.; Salzman, A.L. Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages using a manganese mesoporphyrin superoxide dismutase mimetic and peroxynitrite scavenger. Fed. Eur Biochem. Soc. Lett., 1996, 381(1-2), 82-86.
85. Liang, L.P.; Huang, J.; Fulton, R.; Day, B.J., Patel, M. An orally active catalytic metalloporphyrin protects against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine neurotoxicity in vivo. J. Neurosci., 2007, 27(16), 4326-4333.
86. Rosenthal, R.A.; Huffman, K.D.; Fisette, L.W.; Damphousse, C.A.; Callaway, W.B.; Malfroy, B.; Doctrow, S.R. Orally available Mn porphyrins with superoxide dismutase and catalase activities. J. Biol. Inorg. Chem., 2009, 14(6), 979-991.
87. Patel, M.; Day, B.J. Metalloporphyrin class of therapeutic catalytic antioxidant. Trends Pharm. Sci., 1999, 20(9), 359-364.
88. Day, B.J. Catalytic antioxidants: a radical approach to new therapeutics. Drug Discov. Today, 2004, 9(13), 557-566.
89. 5+) a powerful and potentially useful superoxide dismutase mimic. J. Biol. Chem., 1998, 273(38), 24521-24528.
90. Mackensen, G.B.; Patel, M.; Sheng, H.; Calvi, C; Batinic-Haberle, I.; Day, B.J.; Liang, L.P.; Fridovich, I.; Crapo, J.D.; Pearlstein, R.D.; Warner, D.S. Neuroprotection from delayed post-ischemic administration of a metalloporphyrin catalytic antioxidant. J. Neurosci., 2001, 21(13), 4582-4592.
91. Melov, S.; Doctrow, S.R.; Schneider, J.A.; Haberson, J.M; Patel, M.; Coskun, P.E.; Huffman, K.; Wallace, D.C.; Malfroy, B. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J. Neurosci. 2001 21(21), 8348-8353.
92. Oury, T.D.; Thakker, K.; Menache, M.; Chang, L.Y.; Crapo, J.D.; Day, B.J. Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant metalloporphyrin. Am. J. Respir. Cell. Mol. Biol., 2001, 25(2), 164-169.
93. Vujaskovic, Z.; Batinic-Haberle, I.; Rabbani, Z.N.; Feng, Q.F.; Kang, S.K.; Spasojevic, I.; Samulski, T.V.; Fridovich, I.; Dewhirst, M.W.; Anscher, M.S. A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Radic. Biol. Med., 2002, 33(6), 857-863.
94. 2, inhibits apoptosis, and acts as a radiation mitigator in vivo. ACS Med. Chem. Lett., 2011, 2(11), 814-817.
95. Pearlstein, R.D.; Higuchi, Y.; Moldovan, M.; Johnson, K.; Fukuda, S.; Gridley, D.S.; Crapo, J.D.; Warner, D.S.; Slater, J.M. Metalloporphyrin antioxidants ameliorate normal tissue radiation damage in rat brain. Int J. Radiat. Biol., 2010, 86(2), 145-163.
96. Grosser, T.; Fries, S.; FitzGerald, G. A. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J. Clin. Invest., 2006, 116(1), 4-15.
97. Mao, J.; Price, D. D.; Mayer, D. J. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain, 1995, 62(3), 259-274.
98. Foley, K. M. Misconceptions and controversies regarding the use of opioids in cancer pain. Anticancer Drugs, 1995, 6(Suppl. 3), 4-13.
99. Salvemini, D.; Neumann, W L. Peroxynitrite: a strategic linchpin of opioid analgesic tolerance. Trends Pharmacol. Sci., 2009, 30(4), 194-202.
100. Janes, K.; Neumann, W.L.; Salvemini, D. Anti-superoxide and anti- peroxynitrite strategies in pain suppression. Biochim. Biophys. Acta, 2012, 1822(5), 815-821.
101. Muscoli, C; Cuzzocrea, S.; Ndengele, M.M.; Mollace, V.; Porreca, F.; Fabrizi, F.; Esposito, E.; Masini, E.; Matuschak, G.M.; Salvemini, D. Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice. J. Clin. Invest., 2007, 117(11), 3530-3539.
102. Mahammed, A.; Gross, Z. Iron and manganese corroles are potent catalysts for the decomposition of peroxynitrite. Angew. Chem. Int. Ed., 2006, 45(39), 6544-6547.
103. Haber, A.; Mahammed, A.; Fuhrman, B.; Volkova, N.; Coleman, R.; Hayek, T.; Aviram, M.; Gross, Z. Amphiphilic/bipolar metallocorroles that catalyze the decomposition of reactive oxygen and nitrogen species, rescue lipoproteins from oxidative damage, and attenuate atherosclerosis in mice. Angew. Chem. Int. Ed., 2008, 47(41), 7896-7900.
104. Gershman, Z.; Goldberg, I.; Gross, Z. DNA binding and catalytic properties of positively charged corroles. Angew. Chem. Int. Ed., 2007, 46(23), 4320-4324.
105. Okun, Z.; Kupershmidt, L.; Amit, T.; Mandel, S.; Bar-Am, O.; Youdim, M. B. H.; Gross, Z. Manganese corroles prevent intracellular nitration and subsequent death of insulin-producin cells. ACS Chem. Biol., 2009, 4(11), 910-914.
106. Kupershmidt, L.; Okun, Z.; Amit, T.; Mandel, S.; Saltsman, I.; Mahammed, A.; Bar-Am, O.; Youdim, M. B. H.; Gross, Z.; Youdim, M. B. H. Metallocorroles as as cytoprotective agents against oxidative and nitrative stress in cellular models of neurodegeneration. J. Neurochem., 2010, 113(2), 363-373.
107. Eckshtain, M.; Zilbermann, I.; Mahammed, A.; Saltsman, I.; Okun, Z.; Maimon, E.; Cohen, H.; Meyerstein, D.; Gross, Z. Superoxide dismutase activity of corrole metal complexes. Dalton. Trans., 2009, 7879-7882.
108. Kanamori, A.; Catrinescu, M.-M.; Mahammed, A.; Gross, Z.; Levin, L. A. Neuroprotection against superoxide anion radical by metallocorrole in cellular and murine models of optic neuropathy. J. Neurochem., 2010, 114(2), 488-498.
109. Rausaria, S.; Kamadulski, A.; Rath, N.P.; Bryant, L.; Chen, Z.; Salvemini, D.; Neumann, W.L. Manganese(III) complexes of Bis(hydroxyphenyl) dipyrromethenes are potent orally active proxynitrite scavengers. J. Am. Chem. Soc, 2011, 1338(12), 4200-4203.