Reactive oxygen species generation through NADH oxidation by 6-formylpterin derivatives in the dark.
6-formylpterin (6FP) has been reported to produce reactive oxygen species (ROS) such as *O2- and H2O2 from O2 in the presence of NADH under light condition. In the present study, we prepared a variety of 6FP derivatives and found that 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridin-4-one and 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-methylpteridin-4-one, in which the 2-amino groups are modified by a dimethylaminomethylene group and the 3-positions by pivaloyl and methyl groups and 2-amino-6-formyl-3-methylpteridin-4-one in which the amino group at the 2-position is free and the 3-position is modified by a methyl group generated H2O2 from O2 on oxidation of NADH to NAD+ in the dark. However, 6FP and 2-(N,N-dimethylaminomethyleneamino)-6-formylpteridin-4-one, in which the 3-position is free did not yield H2O2. These results indicate that modification of the 3-position is essential to make the activities of 6FP available in the dark and would be suggestive for designing pharmaceutical compounds that generate appropriate and controllable amounts of ROS in vivo.
Nonogawa
Mitsuru
M
Institute of Advanced Energy, Department of Anesthesia, Kyoto University Hospital, Gokasho, Uji 611-0011, Japan.
Pack
Seung Pil
SP
Arai
Toshiyuki
T
Endo
Nobuyuki
N
Sommani
Piyanart
P
Kodaki
Tsutomu
T
Makino
Keisuke
K
D003624:Darkness; D004578:Electron Spin Resonance Spectroscopy; D006861:Hydrogen Peroxide / Q000737:chemistry; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry*; D010084:Oxidation-Reduction / Q000528:radiation effects; D010100:Oxygen / Q000737:chemistry; D011622:Pterins / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013997:Time Factors
D011622:Pterins; D017382:Reactive Oxygen Species; D009243:NAD; C005926:2-amino-4-hydroxy-6-formylpteridine; D006861:Hydrogen Peroxide; D010100:Oxygen