Structural and functional analogs of CuZn superoxide dismutase inhibit rat brain nitric oxide synthase by interference with the reductase (diaphorase) domain
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- 作者：Mayer ; Bernd ; Pfeiffer ; Silvia ; Leopold ; Eva ; Mü ; ller ; Jö ; rg ; Weser ; Ulrich ; Schmidt ; Kurt
- 关键词：Nitric oxide synthase inhibitor ; NADPH-diaphorase ; Superoxide dismutase mimics ; Copper complexes ; Rat brain
- 刊名：Neuroscience Letters
- 出版年：1996
- 出版时间：May 17, 1996
- 年：1996
- 卷：209
- 期：3
- 页码：169-172
- 全文大小：381 K
文摘
Copper complexes with superoxide dismutase (SOD) activity show a wide range of pharmacological activities. We have investigated the effect of ([N,N′-bis(2-pyridylmethylene)-1,4-butanediamine]-(N,N′,N″,N
))-Cu(II)-chloride (Cu-PuPy) and {[N,N′-bis(2-pyridylphenyl)methylene-1,4-butanediamine]-(N,N′,N″,N)}-Cu(II)-chloride (Cu-PuPhePy) on the multiple catalytic functions of rat brain NO synthase (NOS). Both drugs inhibited the formation of l-citrulline as well as the enzymatic reduction of cytochrome c. The uncoupled oxidation of NADPH, catalyzed by neuronal NOS in the absence of l-arginine, was inhibited by Cu-PuPy but stimulated by Cu-PuPhePy, suggesting that the phenyl-substituted compound acts as a parasitic electron acceptor. Our data identify copper complexes with SOD mimicking activity as a novel class of neuronal NOS inhibitors blocking the reductase (diaphorase) activity of the enzyme.
))-Cu(II)-chloride (Cu-PuPy) and {[N,N′-bis(2-pyridylphenyl)methylene-1,4-butanediamine]-(N,N′,N″,N)}-Cu(II)-chloride (Cu-PuPhePy) on the multiple catalytic functions of rat brain NO synthase (NOS). Both drugs inhibited the formation of l-citrulline as well as the enzymatic reduction of cytochrome c. The uncoupled oxidation of NADPH, catalyzed by neuronal NOS in the absence of l-arginine, was inhibited by Cu-PuPy but stimulated by Cu-PuPhePy, suggesting that the phenyl-substituted compound acts as a parasitic electron acceptor. Our data identify copper complexes with SOD mimicking activity as a novel class of neuronal NOS inhibitors blocking the reductase (diaphorase) activity of the enzyme.