Publications (16)59.63 Total impact
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Article: A new series of ferrocifen derivatives, bearing two aminoalkyl chains, with strong antiproliferative effects on breast cancer cells
New Journal of Chemistry 02/2013; · 2.61 Impact Factor -
Dataset: Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells
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Dataset: Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells
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Article: A rhenium tris-carbonyl derivative as a single core multimodal probe for imaging (SCoMPI) combining infrared and luminescent properties.
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ABSTRACT: A rhenium tris-carbonyl derivative has been designed to couple infrared and luminescent detection in cells. Both spectroscopies are consistent with one another; they point out the reliability of the present SCoMPI (for Single Core Multimodal Probe for Imaging) for bimodal imaging and unambiguously indicate a localization at the Golgi apparatus in MDA-MB-231 breast cancer cells.Chemical Communications 06/2012; 48(62):7729-31. · 6.17 Impact Factor -
Article: Synthesis, cytotoxicity, and COMPARE analysis of ferrocene and [3]ferrocenophane tetrasubstituted olefin derivatives against human cancer cells.
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ABSTRACT: Herein we report the antiproliferative effects of a series of 28 compounds against the MDA-MB-231 breast cancer cell line, including the synthesis of seven new [3]ferrocenophanyl and four new ferrocenyl compounds. For each p-R-phenyl substitution pattern investigated, the [3]ferrocenophanyl derivatives were more cytotoxic than the corresponding ferrocenyl derivative, with the highest activity found for compounds with protic substituents. Theoretical calculations of the HOMO-LUMO gap for the molecules in the Fe³(+) oxidation state suggest a higher reactivity for the [3]ferrocenophanyl derivatives. A lead compound from each series, a [3]ferrocenophanyl and a ferrocenyl compound, possessing two phenol groups, were screened against the NCI/DTP 60-cell-line panel. The mean activity over all cell lines was better than cisplatin for both compounds, and both compounds showed subpanel selectivity for leukemia, CNS cancer, and renal cancer. Low systemic toxicity and lack of interaction with DNA (when in the reduced form), suggest that the compounds may act as prodrugs.ChemMedChem 12/2010; 5(12):2039-50. · 3.15 Impact Factor -
Article: Subcellular IR imaging of a metal-carbonyl moiety using photothermally induced resonance.
Angewandte Chemie International Edition 10/2010; 50(4):860-4. · 13.45 Impact Factor -
Article: Organometallic cyclic polyphenols derived from 1,2-(alpha-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells.
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ABSTRACT: We have previously shown that achiral ferrocenyl diphenol butene derivatives are strong antitumor agents against both hormone-dependent and -independent breast cancer cell lines. We report now examples of a new series of two planar chiral diphenol derivatives, namely 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]trimethylene] ferrocene (4), and 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]tetramethylene]ferrocene (5). They were prepared under racemic form from a McMurry coupling reaction with 30% and 16% yields, respectively. Compound 5 gave crystals suitable for X-ray structural analysis. Compounds 4 and 5 were tested for ERalpha and ERbeta affinity, lipophilicity, and proliferative/antiproliferative effects against the hormone-dependent breast cancer cell line MCF-7, and the hormone-independent breast cancer cell line MDA-MB-231. Both compounds exhibit better affinity for ERbeta (16.4 +/- 0.1, and 7.0 +/- 0.4, respectively) than for ERalpha (6.4 +/- 0.2, and 6.6 +/- 0.2). The test on hormone-independent breast cancer cell line MDA-MB-231 showed that 4 with a 5-membered ring gives an IC50 value of 2.7 microM while with 5 in which the ring has 6 carbons, the value is reduced to IC50 = 1.23 microM.Dalton Transactions 08/2010; 39(32):7444-50. · 3.84 Impact Factor -
Article: A [3]ferrocenophane polyphenol showing a remarkable antiproliferative activity on breast and prostate cancer cell lines.
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ABSTRACT: We have previously shown that modification of polyphenols with a ferrocenyl group can dramatically enhance their cytotoxicity. We now present two new [3]ferrocenophane compounds, one of which has an antiproliferative effect seven times stronger than the corresponding noncyclic species, with IC50 values of 90 and 94 nM on hormone-independent MDA-MB-231 breast and PC-3 prostate cancer cell lines, respectively. Solubility studies in water using methylated beta-cyclodextrin and electron transfer studies are also presented.Journal of Medicinal Chemistry 07/2009; 52(15):4964-7. · 4.80 Impact Factor -
Article: Role of aromatic substituents on the antiproliferative effects of diphenyl ferrocenyl butene compounds.
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ABSTRACT: 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.Dalton Transactions 06/2009; · 3.84 Impact Factor -
Article: Synthesis and Structure Activity Relationship of Organometallic Steroidal Androgen Derivatives
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ABSTRACT: We present here the synthesis and the structure activity relationship of a series of organometallic complexes of the steroidal androgens testosterone and dihydrotestosterone (DHT) substituted at the C-17 position of the steroid skeleton with an ethynyl substituent grafted with various sandwich or semisandwich organometallic units [ferrocenyl, (η5-C5H4)-Re(CO)3, (η5-C5H4)-Mn(CO)3, (η6-C6H5)-Cr(CO)3] and of 3β-androstanediol substituted at C-16 and C-17 respectively by a ferrocenyl vinyl and a ferrocenyl ethynyl unit. In contrast to the estradiol series, there are currently very few examples of organometallic steroidal androgens in the literature. The ethynyltestosterone derivatives were obtained via a Stille coupling reaction between the appropriate iodo-organometallics and 17β-ethynyltestosterone stannyl derivatives. The ethynyl-DHT derivatives were synthesized by addition of the corresponding acetylide to the C-17 carbonyl of the steroid. The crystal structures of two ferrocenyl and one rhenium complexes were determined by X-ray diffraction and had confirmed that the organometallic moiety points toward the α face of the steroid skeleton. All the complexes retain a modest affinity for the androgen receptor. The ferrocenyl derivatives of ethynyl testosterone, 8 and 12, show a strong antiproliferative effect on the hormone-independent prostate cancer cells PC-3 with IC50 values of respectively 4.7 and 8.3 μM. These values are very similar, for 12, or slightly better, for 8, than those found recently for the most active ferrocenyl derivative of the nonsteroidal antiandrogen nilutamide (IC50 value of 5.4 μM). The ferrocenyl complexes described here are the first examples of organometallic steroidal androgens possessing a strong antiproliferative activity on prostate cancer cells.03/2009; -
Article: Synthesis and structure-activity relationships of ferrocenyl tamoxifen derivatives with modified side chains.
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ABSTRACT: We report here the synthesis and cell-proliferation properties of derivatives of the breast cancer drug tamoxifen, in which the -O(CH(2))(2)N(CH(3))(2) side chain, responsible for the drug's antiestrogenic properties, has been modified by a ferrocenyl moiety. We recently reported the diphenol compound 5, in which this amino chain had been replaced with an acyl-ferrocenyl (-O(CH(2))(2)C(O)[(eta(5)-C(5)H(4))FeCp]) group, and which showed antiproliferative effects against both the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. We now report the results of a structure-activity relationship (SAR) study, in which the lateral chain length has been varied, the ketone group has been omitted, and the number of phenol groups has been varied. Compounds 1-4, with a side chain lacking the carbonyl function (-O(CH(2))(n)[(eta(5)-C(5)H(4))FeCp], n = 1-4) and which show a decreasing affinity for ERalpha (ER = estrogen receptor) with increasing chain length, act as estrogens on MCF-7 cells, and mild cytotoxics on PC-3 prostate cancer cells, with IC(50) values around 10 microM. The two monophenolic derivatives of 2, 2 a and 2 b, which show a reduced affinity for ERalpha compared to 2, are also estrogenic, but are only slightly cytotoxic. Finally, we have reexamined compound 5 and discovered that its antiproliferative effect against the MCF-7 cell line does not arise from antiestrogenicity as we had originally suspected, but by means of a cytotoxic pathway. This compound is also sensitive to the number of phenol groups as cell death is diminished when one of the hydroxyl groups is omitted (5 a and 5 b). Molecular modeling studies of the ligand-ERalpha binding stability are broadly consistent with the experimental binding affinity results for compounds 2, 2 a, 2 b, 5, 5 a, and 5 b. Electrochemical experiments show that 1-4, 2 a, and 2 b are stable to oxidation on the electrochemical timescale, unlike 5, 5 a, and 5 b, and that cytotoxicity is related to less positive phenol oxidation potentials. The SAR study shows that the presence of a ketone group and two phenol groups is necessary for strong receptor binding and cytotoxic effects, and that all compounds are estrogenic, despite the presence of a bulky side chain.Chemistry 01/2009; 15(3):684-96. · 5.93 Impact Factor -
Article: Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide.
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ABSTRACT: We present here the first synthesis of organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, bearing a ferrocenyl substituent at position N(1) or at C(5) of the hydantoin ring; for comparison, we also describe the C(5) p-anisyl organic analogue. All of these complexes retain a modest affinity for the androgen receptor. The N-substituted complexes show a weak or moderate antiproliferative effect (IC 50 around 68 microM) on hormone-dependent and -independent prostate cancer cells, while the C(5)-substituted compounds exhibit toxicity levels 10 times higher (IC 50 around 5.4 microM). This strong antiproliferative effect is probably due to a structural effect linked to the aromatic character of the ferrocene rather than to its organometallic feature. In addition, it seems connected to a cytotoxic effect rather than an antihormonal one. These results open the way toward a new family of molecules that are active against both hormone-dependent and hormone-independent prostate cancer cells.Journal of Medicinal Chemistry 04/2008; 51(6):1791-9. · 5.25 Impact Factor -
Article: The presence of a ferrocenyl unit on an estrogenic molecule is not always sufficient to generate in vitro cytotoxicity.
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ABSTRACT: We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the standard molecule in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on molecules with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in vitro, we prepared complexes derived from estradiol with a ferrocenyl substituent at positions 7alpha and 17alpha. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12 %). At low concentrations (0.1-1 microM) the complexes show an estrogenic effect in vitro equivalent to that of estradiol on hormone-dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone-independent (MDA-MB-231) breast cancer cells. At high concentrations (up to 50 microM) the 17alpha-ethynylferrocenyl estradiol and 7alpha-ferrocenylmethylthio estradiol become cytotoxic (IC(50)=13.2 microM and 18.8 microM, respectively) while the 17alpha-ferrocenylestradiol remains non toxic. The low toxicity of these compounds support our hypothesis that electronic communication between the ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key parameter in the generation of cytotoxic effects at submicromolar concentrations.ChemMedChem 12/2006; 1(11):1275-81. · 3.15 Impact Factor -
Article: Ferrocenyl compounds possessing protected phenol and thiophenol groups: Synthesis, X-ray structure, and in vitro biological effects against breast cancer
Journal of Organometallic Chemistry 693:1716-1722. · 2.38 Impact Factor -
Article: Comparative toxicity of [3]ferrocenophane and ferrocene moieties on breast cancer cells
Tetrahedron Letters 51(1):118-120. · 2.68 Impact Factor -
Article: The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-l-ene compounds against breast cancer cells
Journal of Organometallic Chemistry 694(6):895-901. · 2.38 Impact Factor
Top co-authors
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Institutions
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2009–2010
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École nationale supérieure de chimie de Paris
Paris, Ile-de-France, France
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2006
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Chimie ParisTech
Paris, Ile-de-France, France
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