Abstract
We have isolated two bisphenolic compounds (4 and 5) that have a marked effect on K+ and Na+ concentrations in human cells from commercial preparations of the pH indicator dye phenol red (phenolsulfonphthalein). We used a bioassay to identify active chromatographic fractions from the lipophilic impurities present in phenol red, and we determined the structure of two active components (4 and 5) by 1H and 13C NMR and mass spectrometry. When added to human fibroblasts in serum-free medium, the bisphenol fluorene derivative 9,9-bis(4'-hydroxyphenyl)-3-hydroxyfluorene (5) produced a rapid loss of K+ and a gain of Na+, at low concentrations, with an EC50 between 30 and 60 ng/mL (80-160 nM). The 2- and 4-hydroxy isomers of the fluorene 5 (i.e., compounds 6 and 7), prepared by synthesis, had similar activity, although compound 6 was somewhat less potent. The bisphenol xanthene derivative 9,9-bis(4'-hydroxyphenyl)xanthene (4) elicited a similar biological response but was less potent than 5-7; it also had a strong effect on cell adhesion, causing release of cells from the plastic substrate at concentrations as low as 2-5 microg/mL (5.5-14 microM). The structures of xanthene (4) and fluorene (5) bisphenols have been confirmed by synthesi...Continue Reading
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Feb 26, 2011·Chemical Communications : Chem Comm·James J CrawfordSamantha A Orr
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