Activation of the aryl hydrocarbon receptor by methyl yellow and related congeners: Structure-activity relationships in halogenated derivatives
Activation of the aryl hydrocarbon receptor by methyl yellow and related congeners: Structure-activity relationships in halogenated derivatives
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DOI：
10.1248/bpb.25.466
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发表时间：
2002-04-01
影响因子：
2
通讯作者：
Saeki, K
中科院分区：
文献类型：
--
作者：
Kato, TA;Matsuda, T;Saeki, K
芳烃受体 (AhR) 是一种配体激活的转录因子，介导许多环境化合物的生物作用。甲基黄（4-二甲基氨基偶氮苯；MY）是一种主要的偶氮染料，通过使用酵母 AhR 信号分析，对结构相关的化合物作为 AhR 配体进行结构-活性关系分析。 23个卤代MY中的卤素取代对AhR配体活性的影响可概括如下：邻位（2'-和6'-位）卤素取代增强，对位（4'-位）取代降低。在2',6'-二氯化MY中观察到配体活性的最大增强（MY的13.5倍），其AhR配体活性非常接近本测定系统中的2,3,7,8-四氯二苯并-对二恶英（TCDD）。在与 MY 结构相关的化合物的研究中，苯甲酰苯胺 (BA) 显示出与偶氮苯和反式二苯乙烯几乎相同的 AhR 配体活性。此外，分子长度与MY相似的4'-氯苯甲酰苯胺通过邻(2')-氯取代增强了AhR配体活性，且2',4'-二氯苯甲酰苯胺的AhR配体活性与2'-氯-MY相似。这些结果表明，在1,2-二苯基-1,2-烯衍生物中，酰胺键相当于-N=N-或-CH=CH-双键，可被AhR识别为配体。
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological action of many environmental compounds. Methyl yellow (4-dimethylaminoazobenzene; MY) is a principal azodye, and structurally related compounds were subjected to analysis of structure-activity relationships as AhR ligands by using a yeast AhR signaling assay. The effects of halogen-substitution among 23 halogenated MYs on the AhR ligand activity can be summarized as follows: enhancement by halogen-substitution at the ortho-position (2'- and 6'-position), and reduction by substitution at the para-position (4'-position). The greatest enhancement of the ligand activity was observed in 2',6'-dichlorinated MY (13.5-fold of MY), and its AhR ligand activity was very close to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the present assay system. In the study of compounds structurally related to MY, benzanilide (BA) showed almost the same AhR ligand activity as azobenzene and trans-stilbene. Furthermore, 4'-chlorobenzanilide, in which the length of the molecule is similar to that of MY, enhanced the AhR ligand activity by ortho(2')-chlorine-substitution, and the AhR ligand activity of 2',4'-dichlorobenzanilide was similar to that of 2'-chloro-MY. These results suggest that the amide bond is equivalent to the -N=N- or -CH=CH- double bond for recognition as the ligand by AhR in 1,2-diphenyl-1,2-ene derivatives.