Bisphenols that stimulate cells to release alkali metal cations: a structure-activity study.
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.
Department of Pediatrics, Jefferson Medical College, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
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D000818:Animals; D019556:COS Cells; D002400:Cathartics / Q000737:chemistry / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000378:metabolism*; D008672:Metals, Alkali / Q000378:metabolism*; D010635:Phenolphthaleins / Q000737:chemistry / Q000494:pharmacology*; D010637:Phenolsulfonphthalein / Q000737:chemistry / Q000494:pharmacology*; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013329:Structure-Activity Relationship
D002400:Cathartics; D002414:Cations, Monovalent; D008672:Metals, Alkali; D010635:Phenolphthaleins; D012414:Rubidium Radioisotopes; D010637:Phenolsulfonphthalein