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硝基芳烃的还原活化与酶抑制:米索硝唑与黄嘌呤氧化酶

Reductive activation of nitroaromatics and enzyme inhibition: misonidazole and xanthine oxidase.

作者信息

Raleigh J A, Liu S F, Shum F Y

出版信息

Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):701-4. doi: 10.1016/0360-3016(82)90716-7.

DOI:10.1016/0360-3016(82)90716-7
PMID:6896706
Abstract

Reductive activation of misonidazole and misondiazole acetate, a simple derivative, in the presence of xanthine oxidase causes inactivation of the enzyme. The inactivation is not accompanied by binding of the misonidazole to the enzyme. The nitroreductase activity of xanthine oxidase is inhibited as measured by the reduction of 3,5-dinitrobenzonitrile (DNBN). Cysteine does not appear to protect against the enzyme inactivation by misonidazole but, by itself, cysteine has a strong stimulating effect on the reduction of DNBN. The possible significance of these reactions to the toxicity of misonidazole are discussed.

摘要

在黄嘌呤氧化酶存在的情况下,甲硝唑和一种简单衍生物醋酸米索硝唑的还原激活会导致该酶失活。这种失活并不伴随着甲硝唑与酶的结合。通过3,5 - 二硝基苯甲腈(DNBN)的还原测定,黄嘌呤氧化酶的硝基还原酶活性受到抑制。半胱氨酸似乎不能防止甲硝唑对酶的失活作用,但半胱氨酸本身对DNBN的还原有很强的刺激作用。讨论了这些反应对甲硝唑毒性的可能意义。

相似文献

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Reductive activation of nitroaromatics and enzyme inhibition: misonidazole and xanthine oxidase.硝基芳烃的还原活化与酶抑制:米索硝唑与黄嘌呤氧化酶
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):701-4. doi: 10.1016/0360-3016(82)90716-7.
2
Reduction of misonidazole and its derivatives by xanthine oxidase.黄嘌呤氧化酶对米索硝唑及其衍生物的还原作用。
Biochem Pharmacol. 1981 Apr 15;30(8):849-53. doi: 10.1016/s0006-2952(81)80006-8.
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Reductive metabolism and DNA binding of misonidazole.米索硝唑的还原代谢与DNA结合
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Reductive fragmentation of 2-nitroimidazoles in the presence of nitroreductases--glyoxal formation from misonidazole.在硝基还原酶存在下2-硝基咪唑的还原断裂——米索硝唑生成乙二醛
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引用本文的文献

1
Binding of misonidazole to hypoxic cells in monolayer and spheroid culture: evidence that a side-chain label is bound as efficiently as a ring label.米索硝唑在单层和球体培养中与缺氧细胞的结合:侧链标记物与环标记物结合效率相同的证据。
Br J Cancer. 1985 Feb;51(2):229-35. doi: 10.1038/bjc.1985.33.