Mammalian cell toxicity and bacterial mutagenicity of nitrosoimidazoles.
Mammalian cell toxicity and bacterial mutagenicity of nitrosoimidazoles.
复制标题
亚硝基咪唑的哺乳动物细胞毒性和细菌致突变性。
DOI：
10.1016/0006-2952(88)90252-3
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发表时间：
1988
影响因子：
5.8
通讯作者：
Goldman,P
中科院分区：
文献类型：
--
作者：
Ehlhardt,WJ;BeaulieuJr,BB;Goldman,P
It is currently believed that the biological activity of such therapeutic 5-nitroimidazoles as metronidazole is mediated by a short-lived, highly toxic species that arises from nitro group reduction. We found that the 5-nitroimidazole, 1-methyl-4-phenyl-5-nitroimidazole (5-NO2), is at least 1000-fold less cytotoxic for CHO cells and mutagenic for Ames tester strain TA100 than its homologous nitroso compound, 1-methy1-4-phenyl-5-nitrosoimidazole (5-NO). Such evidence, along with previous work showing a similar relative bactericidal potency of these compounds, is consistent with the labile nitrosoimidazole being a biologically active species of the nitroimidazole, and indicates that mammalian cells are very susceptible to such an active form. The high potency of both 5-NO and 1-methyl-4-nitroso-5-phenylimidazole (4-NO), in contrast to the lack of potency of 1-methyl-4-nitro-5-phenylimidazole (4-NO2) relative to 5-NO2, is additional evidence to support the suggestion that the activity of a nitro-imidazole is determined mainly by the ease with which it is reduced.
