Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study.
We studied the scavenging activity of rebamipide, a novel antipeptic ulcer agent, and seven related compounds against hydroxyl radicals using the electron paramagnetic resonance (EPR) spin trapping technique. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was used as a spin trapping agent. We estimated the second order rate constant for the reaction between the agents tested and hydroxyl radical at pH 7.8 by kinetic competition studies. All compounds tested scavenged the hydroxyl radicals with a certain relationship between concentration and scavenging efficacy. A structure-scavenging activity relationship was derived from the kinetic evidence available on the formation and inhibition of the DMPO spin adduct EPR signal of hydroxyl radicals (DMPO-OH). Important determinants for scavenging hydroxyl radicals were the 3,4-double bond of the quinolinone ring in conjunction with a 2-oxo function and the carbonyl portion of the amido group in conjunction with a para-chlorobenzoyl function.
Naito
Y
Y
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Tanigawa
T
T
Sakurai
K
K
Yamasaki
K
K
Uchida
M
M
Kondo
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D001667:Binding, Competitive; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry*; D007700:Kinetics; D008745:Methylation; D011804:Quinolines / Q000737:chemistry; D015363:Quinolones / Q000737:chemistry*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D011804:Quinolines; D015363:Quinolones; D013113:Spin Labels; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D006861:Hydrogen Peroxide; C052785:rebamipide; D000409:Alanine