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首页> 外文期刊>Journal of Medicinal Chemistry >Bisphenols that stimulate cells to release alkali metal cations: a structure-activity study.
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Bisphenols that stimulate cells to release alkali metal cations: a structure-activity study.

机译:刺激细胞释放碱金属阳离子的双酚:结构活性研究。

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摘要

The laxative action of phenolphthalein (5) is believed to result from induction of potassium and water efflux from the colon epithelium. In cultured cells, K+ efflux is promoted by 5 and by a contaminant (1) present in commercial phenol red. Six compounds with chemical structures related to those of 5 and 1 were tested for ability to induce the release of 86Rb from COS-7 cells preloaded with this isotope: 4,4'-(9-fluorenylidene)diphenol (2), 4, 4'-(9-fluorenylidene)dianiline, 4, 4'-(9-fluorenylidene)bisphenoxyethanol, 1,1'-bi-2-naphthol, 4, 4'-biphenol, and bis(4-hydroxyphenyl)methane. With one exception these compounds were all inactive at a concentration of 10 microM. However, 2 caused profound 86Rb efflux at concentrations as low as 100 nM. Concentrations of 5 1-2 orders of magnitude higher were needed to achieve similar levels of activity. The three compounds known to be active in this experimental system share a common feature that is absent in all the inactive compounds: a five-membered ring structure, one of whose carbon atoms is disubstituted with p-hydroxyphenyl residues. Because 2 and 5 are readily available, comparative studies on the mechanism of action of these biphenols at the cellular level can now be undertaken.
机译:酚酞(5)的通便作用被认为是由于结肠上皮诱导钾和水流出引起的。在培养的细胞中,K +外向通过5和商业酚红中的污染物(1)促进。测试了六种具有与5和1的化学结构相关的化学结构的化合物诱导从装有此同位素的COS-7细胞中释放86Rb的能力:4,4'-(9-芴基)二酚(2),4、4 '-(9-芴基)二苯胺,4、4'-(9-芴基)双苯氧基乙醇,1,1'-联-2-萘,4,4'-联苯酚和双(4-羟苯基)甲烷。除了一个例外,这些化合物在10 microM的浓度下均无活性。然而,2在低至100 nM的浓度下引起了明显的86Rb流出。为了达到相似的活性水平,需要高5 1-2个数量级的浓度。已知在该实验系统中具有活性的三种化合物具有一个共同的特征,该特征在所有非活性化合物中均不存在:五元环结构,其中一个碳原子被对羟基苯残基二取代。因为2和5很容易获得,所以现在可以对这些双酚在细胞水平上的作用机理进行比较研究。

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