ARYLHYDROXAMIC ACID BIOACTIVATION VIA ACYL GROUP TRANSFER. STRUCTURAL REQUIREMENTS FOR TRANSACYLATING AND ELECTROPHILE-GENERATING ACTIVITY OF N-(2-FLUORENYL)HYDROXAMIC ACIDS AND RELATED COMPOUNDS
ARYLHYDROXAMIC ACID BIOACTIVATION VIA ACYL GROUP TRANSFER. STRUCTURAL REQUIREMENTS FOR TRANSACYLATING AND ELECTROPHILE-GENERATING ACTIVITY OF N-(2-FLUORENYL)HYDROXAMIC ACIDS AND RELATED COMPOUNDS
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通过酰基转移进行芳基羟肟酸生物活化。
DOI：
10.1002/chin.198249194
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
P. E. Hanna
中科院分区：
文献类型：
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作者：
H. Yeh;P. E. Hanna
报道了12种2V-（2-氟烯基）羟肟酸、N-（2-氟烯基）-N-羟基脲和N-（2-氟烯基）- at -羟基氨基甲酸酯的合成。这些化合物被评估为它们作为部分纯化的仓鼠肝芳基羟肟酸lV， 0-酰基转移酶制剂的底物的能力。以4-氨基偶氮苯为酰基受体，分光光度法测定转酰基化活性，n -乙酰蛋氨酸捕获法测定亲电生成活性。只有jv -乙酰基、tv -丙酰和n -甲基-氧乙酰基衍生物表现出相对较高的活性水平。这些结果与先前报道的关于该酶系统激活所需的酰基的空间和电子特性的结论大致一致。n -羟基-2-乙酰氨基芴失活-酰基转移酶对iv -乙酰基化合物生物活性的抑制程度大于iv -丙酰或iv -甲基羟乙酰基衍生物。7V-（2-氟烯基）乙酰羟肟酸（1；表1）是一种iv -芳基羟肟酸，经代谢激活后可转化为亲电反应物，能够与生物大分子上的亲核位点共价结合。后一过程被认为是1和相关的tv -芳基羟肟酸的毒性和致癌活性的原因。1 n -芳基羟肟酸7V， 0-酰基转移酶
The synthesis of a series of 12 2V-(2-fluorenyl) hydroxamic acids, N-(2-fluorenyl)-N-hydroxyureas, and N-(2-fluorenyl)-AT-hydroxycarbamates is reported. The compounds were evaluated for their ability to serve as substrates for a partially purified hamster hepatic arylhydroxamic acid lV, 0-acyltransferase preparation. Transacylating activity was measured spectrophotometrically with 4-aminoazobenzene as the acyl group acceptor, and electrophile-generating activity was quantified by the N-acetylmethionine trapping assay. Only the JV-acetyl, TV-propionyl, and N-meth-oxyacetyl derivatives exhibited relatively high levels ofactivity as measured by either of the assay methods. These results are generally consistent with previously reported conclusions regarding the steric and electronic characteristics of acyl groups that are required for activation by this enzyme system.,-Acyltransferase inactivation by N-hydroxy-2-acetamidofluorene depressed the bioactivation of the IV-acetyl compound to a greater extent than either the IV-propionyl or IV-methyloxyacetyl derivative.7V-(2-Fluorenyl) acetohydroxamic acid (1; Table I) is an iV-arylhydroxamic acid which, upon metabolic activation, is converted to electrophilic reactants capable of covalent binding to nucleophilic sites on biological macromolecules. The latter process is believedto be responsible for the toxic and carcinogenic activity of 1 and related TV-arylhydroxamic acids. 1 N-Arylhydroxamic acid 7V, 0-acyltransferase