Hopp L, Megee S O, Lloyd J B
Department of Pediatrics, Jefferson Medical College, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
J Med Chem. 1998 Oct 22;41(22):4421-3. doi: 10.1021/jm980315d.
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.
酚酞（5）的泻下作用被认为是由结肠上皮细胞中钾和水外流的诱导所导致的。在培养细胞中，5以及商业酚红中存在的一种污染物（1）可促进钾离子外流。测试了六种化学结构与5和1相关的化合物诱导预加载该同位素的COS-7细胞释放86Rb的能力：4,4'-（9-亚芴基）二酚（2）、4,4'-（9-亚芴基）二苯胺、4,4'-（9-亚芴基）双苯氧基乙醇、1,1'-联-2-萘酚、4,4'-联苯酚和双（4-羟基苯基）甲烷。除一种化合物外，这些化合物在10 microM浓度下均无活性。然而，2在低至100 nM的浓度下可引起显著的86Rb外流。需要比5高1-2个数量级的浓度才能达到类似的活性水平。已知在该实验系统中有活性的三种化合物具有一个共同特征，而所有无活性化合物均不具备该特征：一个五元环结构，其中一个碳原子被对羟基苯基残基双取代。由于2和5很容易获得，现在可以在细胞水平上对这些双酚的作用机制进行比较研究。
