Non-enzymatic glutathione conjugation of 2-nitroso-6-methyldipyrido [1,2-a: 3',2'-d] imidazole (NO-Glu-P-1) in vitro: N-hydroxy-sulfonamide, a new binding form of arylnitroso compounds and thiols.
In order to study the possible detoxification mechanisms of the carcinogenic arylamine, 2-amino-6-methyldipyrido[1,2-a: 3',2'-d]imidazole (Glu-P-1), the in vitro non-enzymatic reaction of 2-nitroso-6-methyldipyrido[1,2-a: 3',2'-d]imidazole (NO-Glu-P-1) with reduced glutathione (GSH) was examined at pH 7.4 under both aerobic and anaerobic conditions. Two GSH-arylamine adducts were isolated and found to contain the Glu-P-1 and GSH moieties in a 1:1 molar ratio via an N-S linkage. Their structures were assigned as sulfinamide (-NH-SO-) and N-hydroxy-sulfonamide (-N(OH)-SO2-) by their behaviour under acidic and basic conditions and by UV-VIS, 1H-NMR, infrared and mass spectrometries. Also, a N-hydroxy-sulfonamide adduct was produced when NO-Glu-P-1 and cysteine were reacted at pH 7.4. The N-hydroxy-sulfonamide structure is a new binding form between arylnitroso compounds and thiols. The formation of these adducts may also take place in vivo as a detoxification of toxic arylamines since GSH is abundant in organs such as liver or kidney.
Umemoto
A
A
National Cancer Center Research Institute, Tokyo, Japan.
Grivas
S
S
Yamaizumi
Z
Z
Sato
S
S
Sugimura
T
T
D002851:Chromatography, High Pressure Liquid; D003545:Cysteine; D004355:Drug Stability; D005978:Glutathione; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009603:Nitroso Compounds; D013449:Sulfonamides; D013452:Sulfonium Compounds
D009603:Nitroso Compounds; D013449:Sulfonamides; D013452:Sulfonium Compounds; C042871:2-nitroso-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D005978:Glutathione; D003545:Cysteine