Chemical and biological properties of acetyl derivatives of the hydroxylamino reduction products of metronidazole and dimetridazole.
Chemical and biological properties of acetyl derivatives of the hydroxylamino reduction products of metronidazole and dimetridazole.
复制标题
甲硝唑和二甲硝唑羟氨基还原产物的乙酰基衍生物的化学和生物学特性。
DOI：
10.1016/0006-2952(87)90187-0
复制
发表时间：
1987
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
甲硝唑及其相关的5-硝基咪唑经过硝基的明显还原，产生5-羟胺咪唑等活性物质。为了确定这些物种的作用，我们寻求了通过催化还原甲硝唑、二甲硝唑和氟硝唑来制备它们的方法。虽然它们各自的5-羟胺咪唑太不稳定，无法直接分离，但它们的iro， n -二乙酰基衍生物是可分离的。其中，二甲硝唑衍生的羟胺的二乙酰衍生物O， n -二乙酰-1,2-二甲基-5-羟胺咪唑（DiacDMH）被用于进一步研究。通过酶解酰化，将二甲基咪唑转化为单乙酰基衍生物乙酰-1,2-二甲基-5-羟胺咪唑（AcDMH）。检测了二甲基苯二胺和二甲基苯二胺对脆弱拟杆菌、产气荚膜梭菌和大肠杆菌SR58等菌株的杀菌活性，这些菌株已知对二甲基苯二胺敏感，也检测了多种其他细菌的杀菌活性。即使在脱乙酰酶存在的情况下，也没有检测到杀菌活性。由于5-羟胺咪唑本身不能在这些细菌培养中形成，因此5-硝基咪唑的羟胺功能是否具有杀菌活性仍不确定。
Metronidazole and related 5-nitroimidazoles undergo reduction of their nitro group apparently to produce such reactive species as 5-hydroxylaminoimidazoles. To define the role of these species we have sought ways to prepare them by the catalytic reduction of metronidazole, dimetridazole and flunidazole. Although their respective 5-hydroxylaminoimidazoles were too unstable to be isolated directly, theirO,N-diacetyl derivatives were isolable. Of these, the diacetyl derivative of the hydroxylamine derived from dimetridazole,O,N-diacetyl-1,2-dimethyl-5-hydroxylaminoimidazole (DiacDMH), was used for further study. DiacDMH was converted to its monoacetyl derivative,Nacetyl-1,2-dimethyl-5-hydroxylaminoimidazole (AcDMH), by enzymatic deacylation. Both DiacDMH and AcDMH were examined for bactericidal activity against such strains asBacterioides fragilis, Clostridium perfringens, andEscherichi colistrain SR58, which are known to be sensitive to dimetridazole, as well as a variety of other bacteria. No bactericidal activity was detected, even in the presence of deacetylating enzymes. As the 5-hydroxylaminoimidazole itself could not be shown to form in these bacterial incubations, it remains uncertain whether or not the hydroxylamino functionality of a 5-nitroimidazole has bactericidal activity.