The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells

Printer-friendly version
TitleThe replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells
Publication TypeJournal Article
Year of Publication2009
AuthorsPigeon, P, Top S, Zekri O, Hillard EA, Vessieres A, Plamont MA, Buriez O, Labbe E, Huche M, Boutamine S, Amatore C, Jaouen G
JournalJournal of Organometallic Chemistry
Volume694
Issue6
Pagination895-901
Date PublishedMar
ISBN Number0022-328X
Accession NumberISI:000264064900016
Abstract

We have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ER alpha, and between 0.18% and 15.5% for ER beta, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 mu M) and antiproliferative at high concentrations (10 mu M). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC50 values of 0.8 mu M for 2 and 0.65 mu M for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols. (C) 2008 Elsevier B. V. All rights reserved.

URL<Go to ISI>://000264064900016
DOI10.1016/j.jorganchem.2008.11.035
Short TitleThe replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells
Unit: 
UMR 8640