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.
Hopp
L
L
Department of Pediatrics, Jefferson Medical College, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
Megee
S O
SO
Lloyd
J B
JB
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