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Influence of chlorine or fluorine substitution on the estrogenic properties of 1-alkyl-2,3,5-tris(4-hydroxyphenyl)-1H-pyrroles.
MedLine Citation:
PMID:  23043242     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In continuation of our previous work, several 2,3,5-triarylpyrroles with chlorine or fluorine substituents in the aryl residues were synthesised and tested for estrogen receptor (ER) binding at isolated ERα/ERß receptors (HAP assay) and in transactivation assays using ERα-positive MCF-7/2a as well as U2-OS/ERα and U2-OS/ERß cells. In the competition experiment at ERα the compounds displayed very high relative binding affinities of up to 37 % (determined for 8m), however with restricted subtype selectivity (e.g. ERα/ERβ (8m) = 9). The highest estrogenic potency in ERα-positive MCF-7/2a cells was determined for 2,3,5-tris(2-fluoro-4-hydroxyphenyl)-1-propyl-1H-pyrrole 8m (EC50: 23 nM), while in U2-OS/ERα cells 2-(2-fluoro-4-hydroxyphenyl)-3,5-bis(4-hydroxyphenyl)-1-propyl-1H-pyrrole 8b (EC50 = 0.12 nM) was the most potent agonist, only 30 fold less active than estradiol (E2, EC50 = 0.004 nM). In U2-OS/ERß cells for all pyrroles no transactivation could be observed, which documents that they are selective ERα agonists in cellular systems.
Authors:
Anja Schäfer; Anja Wellner; Martin Strauss; Andreas Schäfer; Gerhard Wolber; Ronald Gust
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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