Comparison of the radical trapping ability of PBN, S-PPBN and NXY-059.
The nitrones alpha-phenyl-N-tert-butyl nitrone (PBN), sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) and disodium 2,4-disulfophenyl-N-tert-butyl nitrone (NXY-059) are neuroprotective in a variety of rodent models. The objective of the current studies was to compare the ability of PBN, S-PBN, and NXY-059 to form radical adducts and to prevent salicylate oxidation in an aqueous system. For the electron spin resonance (ESR) studies, hydroxyl radicals were generated with ultraviolet (UV) light and hydrogen peroxide. Secondary radicals were then produced by the addition of methanol, ethanol, isopropanol, dimethylsulfoxide, tetrahydrofuran or 1,4-dioxane. In addition, competition spin trapping studies were performed using PBN-alpha-(13) C and either S-PBN or NXY-059. In the salicylate studies, PBN, S-PBN and NXY-059 were compared to a variety of other antioxidants and reference compounds (cysteine, glutathione, ascorbate, uric acid, Tempo, Trolox, and Tirilizad) for their ability to prevent 2,3- and 2,5-dihydroxybenzoic acid formation induced by hydroxyl radical generating systems. All 3 nitrones trapped carbon- and oxygen-centered radicals to produce ESR-detectable radical adducts. Each nitrone also prevented salicylate oxidation, with PBN being the most effective. The ability of these 3 nitrones to prevent salicylate oxidation resembled that of most of the other compounds tested.
Maples
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Centaur Pharmaceuticals, Inc. 484 Oakmead Parkway Sunnyvale, CA 94085, USA. kmaples@centpharm.com
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D000975:Antioxidants; D001557:Benzenesulfonates / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000737:chemistry; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction; D020156:Salicylic Acid / Q000737:chemistry; D019097:Spin Trapping; D014466:Ultraviolet Rays
D000975:Antioxidants; D001557:Benzenesulfonates; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; C094272:N-tert-butyl-(2-sulfophenyl)nitrone; C029217:phenyl-N-tert-butylnitrone; C120851:disufenton sodium; D006861:Hydrogen Peroxide; D020156:Salicylic Acid