Bisphenolic compounds that enhance cell cation transport are found in commercial phenol red.
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 synthesis from xanthone and hydroxyfluorenone, respectively, by Friedel-Crafts alkylation with phenol. In the latter case, the desired 3-hydroxyfluorene isomer was formed in situ by rearrangement of the 1-hydroxy isomer.
Kym
P R
PR
Department of Chemistry, University of Illinois, Urbana 61801, USA.
Hummert
K L
KL
Nilsson
A G
AG
Lubin
M
M
Katzenellenbogen
J A
JA
D002412:Cations; D006801:Humans; D017136:Ion Transport; D013058:Mass Spectrometry; D015394:Molecular Structure; D010636:Phenols / Q000032:analysis / Q000494:pharmacology*; D010637:Phenolsulfonphthalein / Q000737:chemistry*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D002412:Cations; D010636:Phenols; D012964:Sodium; D010637:Phenolsulfonphthalein; D011188:Potassium