Linked Life Data

19662309

Source:http://linkedlifedata.com/resource/pubmed/id/19662309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2009-8-7
pubmed:abstractText
We have been exploring the cytotoxic effects of conjugated phenylferrocene systems on breast cancer cells. Complexes with p-OH, p-NH(2), and p-NHC(O)CH(3) substitution show particularly high activity, with IC(50) values in the low or sub micromolar range for both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines. We now present the synthesis, X-ray crystal structures and biochemical studies of analogous halogen or pseudo-halogen para-substituted compounds with R = Cl, (Z)-7a; Br, (Z)-7b; CF(3), (E)-7c; and CN, (E)-7d and (Z)-7d. Lacking hydrogen bonding groups, the compounds have low, but non-zero, relative binding affinity values for the oestrogen receptor alpha (RBA <or= 0.55%) as well as mildly exothermic ligand binding in in silico ER docking experiments. All compounds show estrogenic (proliferative) activity on the MCF-7 cell line. On MDA-MB-231 cells, the cyano complex (Z)-7d shows a reasonable cytotoxic effect (IC(50) = 11 microM), its isomer (E)-7d is only slightly cytotoxic (IC(50) = 60 microM), while the Cl, Br, and CF(3) derivatives have no effect. Cytotoxic properties, while they correlate somewhat with the resonance donating abilities of the substituent, are more strongly dependent on the presence of a proton in the functional group, supporting our prior proposition that electrophilic quinoid forms of the compounds could be active species in the cell. A correlation of the redox potential of the ferrocenyl moiety with the Hammett-Taft constants of the substituents was observed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1477-9226
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4318-26
pubmed:meshHeading
pubmed-meshheading:19662309-Animals, pubmed-meshheading:19662309-Antineoplastic Agents, Hormonal, pubmed-meshheading:19662309-Breast Neoplasms, pubmed-meshheading:19662309-Butanes, pubmed-meshheading:19662309-Cell Line, Tumor, pubmed-meshheading:19662309-Cell Survival, pubmed-meshheading:19662309-Crystallography, X-Ray, pubmed-meshheading:19662309-Electrochemistry, pubmed-meshheading:19662309-Estrogen Receptor alpha, pubmed-meshheading:19662309-Estrogen Receptor beta, pubmed-meshheading:19662309-Female, pubmed-meshheading:19662309-Ferrous Compounds, pubmed-meshheading:19662309-Humans, pubmed-meshheading:19662309-Models, Molecular, pubmed-meshheading:19662309-Molecular Structure, pubmed-meshheading:19662309-Protein Binding, pubmed-meshheading:19662309-Sheep, pubmed-meshheading:19662309-Structure-Activity Relationship, pubmed-meshheading:19662309-Uterus
pubmed:year
2009
pubmed:articleTitle
Role of aromatic substituents on the antiproliferative effects of diphenyl ferrocenyl butene compounds.
pubmed:affiliation
Laboratoire Charles Friedel, UMR CNRS 7223, Ecole Nationale Supérieure de Chimie de Paris, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't