Bis(4-hydroxyphenyl)[2-(phenoxysulfonyl)phenyl]methane: isolation and structure elucidation of a novel estrogen from commercial preparations of phenol red (phenolsulfonphthalein)
Bis(4-hydroxyphenyl)[2-(phenoxysulfonyl)phenyl]methane: isolation and structure elucidation of a novel estrogen from commercial preparations of phenol red (phenolsulfonphthalein)
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双(4-羟基苯基)[2-(苯氧基磺酰基)苯基]甲烷：从酚红（酚磺酞）商业制剂中分离和结构解析新型雌激素
DOI：
10.1021/jm00118a020
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发表时间：
1988
影响因子：
7.3
通讯作者：
Katzenellenbogen,JA
中科院分区：
文献类型：
--
作者：
Bindal,RD;Katzenellenbogen,JA
苯酚磺酞（酚红）是一种广泛添加到细胞培养基中的pH指示染料，其商业制剂具有较弱的雌激素活性，可归因于少量亲脂杂质（约0.002%）。我们对该杂质进行了分离，确定其结构为双（4-羟基苯基）[2-(phenoxysulfonyl) phenyl]甲烷，并以苯酚磺酞为原料合成了该杂质。这种化合物与雌激素受体结合的亲和力是雌二醇的50%；它在体外刺激雌激素反应性乳腺癌细胞的增殖和增加孕酮受体含量，并在体内刺激大鼠子宫增重，但在这些试验中显示的效力仅为雌二醇的0.1-0.2%。我们提出了这种新型雌激素是如何在制备酚醛磺酞过程中产生的。这是一个奇怪的观察结果，在明显缺乏雌激素刺激的情况下，雌激素反应细胞（如MCF-7人类乳腺癌细胞）在培养物中迅速生长，其生长速度通常很少受到雌激素的刺激，如果有的话，但被抗雌激素明显抑制。1 .已对培养环境中可能存在雌激素刺激物质的可能性进行了检查，但严格努力确定用于补充培养基的血清中雌激素或雌激素硫酸盐的残留水平，结果为负re-
Commercial preparations of phenolsulfonphthalein (Phenol Red), a pH indicator dye widely added to cell culture media, have weak estrogenic activity that can be accounted for by a minor lipophilic impurity (ca. 0.002%). We have isolatedthis impurity, determined its structure to be bis (4-hydroxyphenyl)[2-(phenoxysulfonyl) phenyl] methane, and synthesized it from phenolsulfonphthalein. This compound binds to the estrogen receptor with an affinity 50% that ofestradiol; it stimulates the proliferation and increases the progesterone receptor content of estrogen-responsive breast cancer cells in vitro, and it stimulates uterine weightgain in rats in vivo, but shows a potency in these assays only 0.1-0.2% that of estradiol. We suggest how this novelestrogen may be generated during the preparation of phenolsulfonphthalein.It has been a curious observation that, in the apparent absence of estrogenic stimulation, estrogen-responsive cells (such as MCF-7 human breast cancer cells) grow rapidly in cultureat a rate that is often marginally, if at all, stimulated by estrogens, but is markedly suppressed by antiestrogens. 1 The possibility that estrogenic stimulatory substances might be present in the culture milieu has been examined, but rigorous efforts to identify residual levels of estrogens or estrogen sulfates in the serum, used to supplement the culture medium, have given negative re-