By-products produced by the reaction of estrogens with hypochlorous acid and their estrogen activities
By-products produced by the reaction of estrogens with hypochlorous acid and their estrogen activities
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DOI：
10.1248/jhs.52.124
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发表时间：
2006-04-01
影响因子：
--
通讯作者：
Fukazawa, H
中科院分区：
文献类型：
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作者：
Nakamura, H;Shiozawa, T;Fukazawa, H
来自人类和动物的雌激素被认为是环境中内分泌干扰物的一个因素。我们研究了它们的卤代衍生物，这可能是由氯处理在污水处理厂。雌酮（E1）、17 β-雌二醇（E2）、雌三醇（E3）和17 α-乙炔基雌二醇（EE 2）的氯化衍生物通过在有机溶剂中与次氯酸反应而产生，并且当溴离子存在时也产生溴化衍生物。通过MS和NMR光谱法确定了分离的氯化和溴化雌激素的结构。卤代衍生物的雌激素活性通过酵母双杂交测定来测量，所述酵母双杂交测定结合人雌激素受体α（hER α）或青鳉鱼（Oryzias latipes）雌激素受体α（medE-R α）。虽然4-氯雌酮（4-CIE 1）和10-氯-1，4-雌甾二烯-3，17-二酮的活性与E1相似，但2-CIE 1的活性高于E1。和2，4-二氯雌酮（2，4-diClE 1）在hER α激动剂试验中分别约为E1的4/5和1/50。在2，4，16，16-四氯雌酮（2，4，16，16-tetraClE 1）中未检测到活性。E2、E3和EE 2的氯代衍生物的雌激素活性表现出与E1相似的趋势。溴代衍生物的活性略弱于相应的氯化衍生物。然而，许多在2和4位卤化的雌激素仍然具有比双酚A强约10（3）-10（4）倍的活性。
Estrogens that originate from humans and animals are thought of as a factor of endocrine disruptors in the environment. We investigated their halogenated derivatives, which could be produced by chlorine treatment at a sewage treatment plant. The chlorinated derivatives of estrone (E1), 17 beta-estradiol (E2), estriol (E3), and 17 alpha-ethynylestradiol (EE2) were produced by the reaction with hypochlorous acid in organic solvents and also brominated derivatives when bromide ions were present. The structures of chlorinated and brominated estrogens isolated were determined by MS and NMR spectroscopy. The estrogenic activities of the halogenated derivatives were measured by yeast two-hybrid assays incorporating the human estrogen receptor alpha (hER alpha) or medaka fish (Oryzias latipes) estrogen receptor alpha (medE-R alpha). Although the activities of 4-chloroestrone (4-CIE1) and 10-chloro-1,4-estradiene-3,17-dione were similar to those of E1, the activities of 2-CIE1. and 2,4-dichloroestrone (2,4-diClE1) were approximately 4/5 and 1/50 that of E 1, respectively, in an agonist assay for hERa. No activity was detected in 2,4,16,16-tetrachloroestrone (2,4,16,16-tetraClE1). The estrogenicities of chlorinated derivatives of E2, E3, and EE2 showed a similar tendency to that of E1. The brominated derivatives showed slightly weaker activity than the corresponding chlorinated derivatives. However, many estrogens halogenated at the 2 and 4 positions still had activity that was approximately 10(3)-10(4) times stronger than that of bisphenol A.