W. Beck and K. Severin, Biometallorganische Chemie: Ein faszinierendes Forschungsgebiet, Chemie in unserer Zeit, vol.100, issue.639, pp.356-365, 2002.
DOI : 10.1002/1521-3781(200212)36:6<356::AID-CIUZ356>3.0.CO;2-F

A. Sigel and . Sigel, Metal Ions in Life Sciences, 2009.

E. Hegg, Unraveling the Structure and Mechanism of Acetyl-Coenzyme A Synthase, Accounts of Chemical Research, vol.37, issue.10, pp.775-783, 2004.
DOI : 10.1021/ar040002e

J. Jeoung and H. Dobbek, Carbon Dioxide Activation at the Ni,Fe-Cluster of Anaerobic Carbon Monoxide Dehydrogenase, Science, vol.318, issue.5855, pp.1461-1464, 2007.
DOI : 10.1126/science.1148481

P. Lindahl, Nickel-carbon bonds in acetyl-coenzyme A synthases/carbon monoxide dehydrogenases In: Metal-Carbon bonds in enzymes and cofactors, Metal Ions in Life Sciences, vol.6, pp.133-147, 2009.

A. Volbeda and J. Fontecilla-camps, Structure???function relationships of nickel???iron sites in hydrogenase and a comparison with the active sites of other nickel???iron enzymes, Coordination Chemistry Reviews, vol.249, issue.15-16, pp.1609-1619, 2005.
DOI : 10.1016/j.ccr.2004.12.009

F. Armstrong and J. Fontecilla-camps, A Natural Choice for Activating Hydrogen, Science, vol.321, issue.5888, pp.498-499, 2008.
DOI : 10.1126/science.1161326
URL : https://hal.archives-ouvertes.fr/cea-00868635

R. Motterlini and L. Otterbein, The therapeutic potential of carbon monoxide, Nature Reviews Drug Discovery, vol.51, issue.9, pp.728-743, 2010.
DOI : 10.1038/nrd3228

B. Wegiel, . Gallo, . Kg-raman, . Jm-karlsson, . Ozanich et al., Nitric Oxide-Dependent Bone Marrow Progenitor Mobilization by Carbon Monoxide Enhances Endothelial Repair After Vascular Injury, Circulation, vol.121, issue.4, pp.537-548, 2010.
DOI : 10.1161/CIRCULATIONAHA.109.887695

L. Otterbein, Carbon Monoxide: Innovative Anti-inflammatory Properties of an Age-Old Gas Molecule, Antioxidants & Redox Signaling, vol.4, issue.2, pp.309-319, 2002.
DOI : 10.1089/152308602753666361

A. Nakao, N. Choi, and . Murase, Protective effect of carbon monoxide in transplantation, Journal of Cellular and Molecular Medicine, vol.15, issue.3, pp.650-671, 2006.
DOI : 10.2337/diabetes.51.4.994

R. Alberto and . Motterlini, Chemistry and biological activities of CO-releasing molecules (CORMs) and transition metal complexes, Dalton Transactions, vol.71, issue.17, pp.1651-1660, 2007.
DOI : 10.1039/b701992k

B. Mann, Carbon Monoxide: An Essential Signalling Molecule, Top Organomet Chem, vol.32, pp.247-285, 2010.
DOI : 10.1007/978-3-642-13185-1_10

C. Romão, . Wa-blättler, G. Seixas, and . Bernardes, Developing drug molecules for therapy with carbon monoxide, Chemical Society Reviews, vol.203, issue.9, pp.3571-3583, 2012.
DOI : 10.1128/AAC.05571-11

F. Zobi, CO and CO-releasing molecules in medicinal chemistry, Future Medicinal Chemistry, vol.5, issue.2, pp.175-188, 2013.
DOI : 10.4155/fmc.12.196

R. Motterlini, . Be-mann, . Johnson, . Clark, C. Foresti et al., Bioactivity and Pharmacological Actions of Carbon Monoxide-Releasing Molecules, Current Pharmaceutical Design, vol.9, issue.30, pp.2525-2539, 2003.
DOI : 10.2174/1381612033453785

I. Fairlamb, . Lynam, . Be-moulton, . Taylor, P. Ak-duhme-klair et al., ??1-2-Pyrone metal carbonyl complexes as CO-releasing molecules (CO-RMs): A delicate balance between stability and CO liberation, Dalton Transactions, vol.19, issue.33, pp.3603-3605, 2007.
DOI : 10.1039/b707377a

T. Pitchumony, . Spingler, and . Motterlini, Syntheses, structural characterization and CO releasing properties of boranocarbonate [H3BCO2H]??? derivatives, Organic & Biomolecular Chemistry, vol.36, issue.21, pp.4849-4854, 2010.
DOI : 10.1039/c0ob00099j

U. Schatzschneider, PhotoCORMs: Light-triggered release of carbon monoxide from the coordination sphere of transition metal complexes for biological applications, Inorganica Chimica Acta, vol.374, issue.1, pp.19-23, 2011.
DOI : 10.1016/j.ica.2011.02.068

P. Kunz, . Huber, . Rojas, . Schatzschneider, and . Spingler, Tricarbonylmanganese(I) and ??????rhenium(I) Complexes of Imidazol-Based Phosphane Ligands: Influence of the Substitution Pattern on the CO Release Properties, European Journal of Inorganic Chemistry, vol.36, issue.35, pp.5358-5366, 2009.
DOI : 10.1002/ejic.200900650

S. Romanski, . Kraus, . Schatzschneider, . Neudorfl, H. Amslinger et al., Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), Angewandte Chemie International Edition, vol.180, issue.10, pp.2392-2396, 2011.
DOI : 10.1002/anie.201006598

S. Romanski, . Kraus, . Guttentag, . Schlundt, . Rucker et al., Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure???activity relationship study, Dalton Transactions, vol.54, issue.45, pp.13862-13875, 2012.
DOI : 10.1016/j.ccr.2011.12.009

S. Gibaud and G. Jaouen, Arsenic-Based Drugs: From Fowler???s Solution to Modern Anticancer Chemotherapy, Top Organomet Chem, vol.32, pp.1-20, 2010.
DOI : 10.1007/978-3-642-13185-1_1
URL : https://hal.archives-ouvertes.fr/hal-01395677

M. Patra, . Ingram, . Pierroz, . Ferrari, . Spingler et al., ] Derivatives with Remarkable In Vitro Anti-schistosomal Activity, Chemistry - A European Journal, vol.54, issue.7, pp.2232-2235
DOI : 10.1002/chem.201204291

S. Moody, . Perez, . Tc-pan, C. Cj-sarkisian, C. Portocarrero et al., The transcriptional repressor Snail promotes mammary tumor recurrence, Cancer Cell, vol.8, issue.3, pp.197-209, 2005.
DOI : 10.1016/j.ccr.2005.07.009

B. Deroo and K. Korach, Estrogen receptors and human disease, Journal of Clinical Investigation, vol.116, issue.3, pp.561-570, 2006.
DOI : 10.1172/JCI27987DS1

V. Jordan, Tamoxifen: a most unlikely pioneering medicine, Nature Reviews Drug Discovery, vol.20, issue.3, pp.205-213, 2003.
DOI : 10.1038/nrd1031

J. Cázares-marinero, Ferrocenoselenoamidas: síntesis y actividad citotóxica, Thèse du master, pp.1-91, 2010.

A. Gutiérrez-hernández, J. López-cortés, . Mc-ortega-alfaro, J. Mt-ramirez-apan, R. Cázares-marinero et al., Ferrocenylselenoamides: Synthesis, Characterization and Cytotoxic Properties, Journal of Medicinal Chemistry, vol.55, issue.10, pp.4652-4663, 2012.
DOI : 10.1021/jm300150t

J. Spencer, . Amin, . Wang, . Packham, . Ss-syed-alwi et al., Synthesis and Biological Evaluation of JAHAs: Ferrocene-Based Histone Deacetylase Inhibitors, ACS Medicinal Chemistry Letters, vol.2, issue.5, pp.358-362, 2011.
DOI : 10.1021/ml100295v

M. Librizzi, . Longo, . Chiarelli, . Amin, C. Spencer et al., Cytotoxic Effects of Jay Amin Hydroxamic Acid (JAHA), a Ferrocene-Based Class I Histone Deacetylase Inhibitor, on Triple-Negative MDA-MB231 Breast Cancer Cells, Chemical Research in Toxicology, vol.25, issue.11, pp.2608-2616, 2012.
DOI : 10.1021/tx300376h

P. Gund, Three-Dimensional Pharmacophoric Pattern Searching, Prog Mol Subcell Biol, vol.5, pp.117-143, 1977.
DOI : 10.1007/978-3-642-66626-1_4

A. Tropsha and W. Zheng, Identification of the Descriptor Pharmacophores Using Variable Selection QSAR Applications to Database Mining, Current Pharmaceutical Design, vol.7, issue.7, pp.599-612, 2001.
DOI : 10.2174/1381612013397834

D. Bernanrd and . Coop, 2D Conformationally Sampled Pharmacophore:?? A Ligand-Based Pharmacophore To Differentiate ?? Opioid Agonists from Antagonists, Journal of the American Chemical Society, vol.125, issue.10, pp.3101-3107, 2003.
DOI : 10.1021/ja027644m

C. Wermuth, . Cr-ganellin, I. Lindberg, and . Mitscher, Glossary of terms used in medicinal chemistry, pp.1129-1143, 1998.

J. Van-drie, Monty Kier and the origin of the pharmacophore concept, Internet Electron J Mol Des, vol.6, pp.271-279, 2007.

K. Kinzler and . Vogelstein, Gatekeepers and caretakers, Nature, vol.386, issue.6627, pp.761-763, 1997.
DOI : 10.1038/386761a0

D. Hanahan and R. Winberg, The Hallmarks of Cancer, Cell, vol.100, issue.1, pp.57-70, 2000.
DOI : 10.1016/S0092-8674(00)81683-9

A. Finberg and . Tycko, The history of cancer epigenetics, Nature Reviews Cancer, vol.74, issue.2, pp.143-153, 2004.
DOI : 10.1038/nrc1279

P. Jones and S. Baylin, The fundamental role of epigenetic events in cancer, Nat Rev Genet, vol.3, pp.415-428, 2002.

P. Marks, . Ra-rifkind, . Vm-richon, . Breslow, . Miller et al., HISTONE DEACETYLASES AND CANCER: CAUSES AND THERAPIES, Nature Reviews Cancer, vol.1, issue.3, pp.194-202, 2001.
DOI : 10.1038/35106079

J. Bolden, R. Peart, and . Johnstone, Anticancer activities of histone deacetylase inhibitors, Nature Reviews Drug Discovery, vol.106, issue.9, pp.769-784, 2006.
DOI : 10.1038/nrd2133

M. Paris, . Porcelloni, D. Binaschi, and . Fattori, Histone Deacetylase Inhibitors: From Bench to Clinic, Journal of Medicinal Chemistry, vol.51, issue.6, pp.1505-1529, 2008.
DOI : 10.1021/jm7011408

S. Shankar and R. Srivastava, Histone Deacetylase Inhibitors: Mechanisms and Clinical Significance in Cancer: HDAC Inhibitor-Induced Apoptosis, Adv Exp Med Biol, vol.615, pp.261-298, 2008.
DOI : 10.1007/978-1-4020-6554-5_13

. Bs-mann, . Johnson, . Mh-cohen, . Justice, and . Pazdur, FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma, Oncologist, vol.12, pp.1249-1252, 2007.

P. Marks and . Breslow, Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug, Nature Biotechnology, vol.125, issue.1, pp.84-90, 2007.
DOI : 10.1038/nbt1272

A. Bieliauskas, M. Sv-weerasinghe, and . Pflum, Structural requirements of HDAC inhibitors: SAHA analogs functionalized adjacent to the hydroxamic acid, Bioorganic & Medicinal Chemistry Letters, vol.17, issue.8, pp.2216-2219, 2007.
DOI : 10.1016/j.bmcl.2007.01.117

S. Hanessian, . Auzzas, . Giannini, . Marzim, . Cabri et al., ??-Alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: A study of chain-length and stereochemical dependence, Bioorganic & Medicinal Chemistry Letters, vol.17, issue.22, pp.6261-6265, 2007.
DOI : 10.1016/j.bmcl.2007.09.014

S. Belvedere, . Witter, . Yan, . Secrist, T. Richon et al., Aminosuberoyl hydroxamic acids (ASHAs): A potent new class of HDAC inhibitors, Bioorganic & Medicinal Chemistry Letters, vol.17, issue.14, pp.3969-3971, 2007.
DOI : 10.1016/j.bmcl.2007.04.089

C. Botta, . Cabri, . Cini, C. De-cesare, . Fattorusso et al., Oxime Amides as a Novel Zinc Binding Group in Histone Deacetylase Inhibitors: Synthesis, Biological Activity, and Computational Evaluation, Journal of Medicinal Chemistry, vol.54, issue.7, pp.2165-2182, 2011.
DOI : 10.1021/jm101373a

D. Griffith, C. Morgan, and . Marmion, A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity, Chemical Communications, vol.26, issue.44, pp.6735-6737, 2009.
DOI : 10.1039/b916715c

W. Guerrant, J. Patil, A. Canzoneri, and . Oyelere, Dual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors, Journal of Medicinal Chemistry, vol.55, issue.4, pp.1465-1477, 2012.
DOI : 10.1021/jm200799p

A. Mai, . Esposito, S. Sbardellat, and . Massat, A NEW FACILE AND EXPEDITIOUS SYNTHESIS OF N-HYDROXY-N???-PHENYLOCTANEDIAMJDE, A POTENT INDUCER OF TERMINAL CYTODIFFERECNTIATION, Organic Preparations and Procedures International, vol.40, issue.4, pp.391-394, 2001.
DOI : 10.1039/p19750000846

Y. Okunoi, . Horita, . Yonemitsu, T. Shibata, and . Amemiya, A convenient method for the synthesis of macrocyclic tetraamides by double condensation reaction, J Chem Soc Perkin Trans, vol.1, pp.1115-1118, 1984.

L. Kubicova, . Waisser, . Kunes, . Kralova, . Odlerova et al., Synthesis of N,N???-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity, Molecules, vol.5, issue.5, pp.714-726, 2000.
DOI : 10.3390/50500714

T. Windholz and J. Clements, Proximity Effects in the Decomposition of Mixed Dicarboxylic???Carbonic Anhydrides, The Journal of Organic Chemistry, vol.29, issue.10, pp.3021-3023, 1964.
DOI : 10.1021/jo01033a055

V. Delfosse, M. Grimaldi, . Pons, . Boulahtouf, . Le-maire et al., Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes, Proceedings of the National Academy of Sciences, vol.109, issue.37, pp.14930-4935, 2012.
DOI : 10.1073/pnas.1203574109
URL : https://hal.archives-ouvertes.fr/inserm-00726779

S. Top, . Vessières, . Leclerq, . Quivy, . Tang et al., Synthesis, Biochemical Properties and Molecular Modelling Studies of Organometallic Specific Estrogen Receptor Modulators (SERMs), the Ferrocifens and Hydroxyferrocifens: Evidence for an Antiproliferative Effect of Hydroxyferrocifens on both Hormone-Dependent and Hormone-Independent Breast Cancer Cell Lines, Chemistry - A European Journal, vol.9, issue.21, pp.5223-5236, 2003.
DOI : 10.1002/chem.200305024

M. Dokmanovic and P. Marks, Prospects: Histone deacetylase inhibitors, Journal of Cellular Biochemistry, vol.15, issue.2, pp.293-304, 2005.
DOI : 10.1002/jcb.20532

J. Somoza, . Skene, C. Katz, . Mol, . Ho et al., Structural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases, Structure, vol.12, issue.7, pp.1325-1334, 2004.
DOI : 10.1016/j.str.2004.04.012

. Enzo-life and . Sciences, enzolifesciences.com/BML-AK500/fluor-de-lys-hdac- fluorometric-activity-assay-kit, 2013.

M. Yoshida, . Kijima, T. Akita, and . Beppu, Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatine A, J Biol Chem, vol.265, pp.17174-17179, 1990.

P. Lombardi, . Cole, D. Dowling, and . Christianson, Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes, Current Opinion in Structural Biology, vol.21, issue.6, pp.735-743, 2011.
DOI : 10.1016/j.sbi.2011.08.004

D. Griffith, C. Parker, and . Marmion, Enzyme Inhibition as a Key Target for the Development of Novel Metal-Based Anti-Cancer Therapeutics, Anti-Cancer Agents in Medicinal Chemistry, vol.10, issue.5, pp.354-370, 2010.
DOI : 10.2174/1871520611009050354

D. Dowling, . Gattis, D. Ca-fierke, and . Christianson, Structures of Metal-Substituted Human Histone Deacetylase 8 Provide Mechanistic Inferences on Biological Function,, Biochemistry, vol.49, issue.24, pp.5048-5056, 2010.
DOI : 10.1021/bi1005046

B. Tait, . Ke-mdlalose, and I. Taljaard, The extraction of some metal ions by LIX 1104 dissolved in toluene, Hydrometallurgy, vol.38, issue.1, pp.1-6, 1995.
DOI : 10.1016/0304-386X(94)00041-Z

M. Miller, Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogs, Chemical Reviews, vol.89, issue.7, pp.1563-1579, 1989.
DOI : 10.1021/cr00097a011

D. Vincent, M. Schwal, and . Vincent, Analysis of cardiotonic heterosides by the color reaction with hydroxylamine and ferric chloride, Annales Pharm Françaises, vol.17, pp.579-584, 1959.

T. Abbas and . Dutta, p21 in cancer: intricate networks and multiple activities, Nature Reviews Cancer, vol.23, issue.6, pp.400-414, 2009.
DOI : 10.1038/nrc2657

W. El-deiry, T. Tokino, . Velculescu, . Db-levy, . Parsons et al., WAF1, a potential mediator of p53 tumor suppression, Cell, vol.75, issue.4, pp.817-825, 1993.
DOI : 10.1016/0092-8674(93)90500-P

. Vm-richon, . Sandhoff, P. Ra-rifkind, and . Marks, Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation, Proceedings of the National Academy of Sciences, vol.97, issue.18, pp.10014-10019, 2000.
DOI : 10.1073/pnas.180316197

C. Gui, . Ngo, . Xu, P. Vm-richon, and . Marks, Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1, Proceedings of the National Academy of Sciences, vol.101, issue.5, pp.1241-1246, 2004.
DOI : 10.1073/pnas.0307708100

M. Ocker and R. Schneider-stock, Histone deacetylase inhibitors: Signalling towards p21cip1/waf1, The International Journal of Biochemistry & Cell Biology, vol.39, issue.7-8, pp.1367-1374, 2007.
DOI : 10.1016/j.biocel.2007.03.001

Y. Sowa, . Orita, . Minimikawa, . Nakano, . Mizuno et al., Histone Deacetylase Inhibitor Activates the WAF1/Cip1 Gene Promoter through the Sp1 Sites, Biochemical and Biophysical Research Communications, vol.241, issue.1, pp.142-150, 1997.
DOI : 10.1006/bbrc.1997.7786

R. Margueron, . Licznar, . Lazennec, . Vignon, and . Cavaillès, Oestrogen receptor alpha increases p21(WAF1/CIP1) gene expression and the antiproliferative activity of histone deacetylase inhibitors in human breast cancer cells, Journal of Endocrinology, vol.179, issue.1, pp.41-53, 2003.
DOI : 10.1677/joe.0.1790041

D. Can, N. Hw-peindy, . Dongo, . Spingler, . Schmutz et al., The [(Cp)M(CO) 3 ](M=Re, 99m Tc) building block for imaging agents and bioinorganic probes: perspectives and limitations, Chem Biodiversity, vol.2012, issue.9, pp.1849-1866

D. Minick, J. Frenz, M. Patrick, and D. Brent, A comprehensive method for determining hydrophobicity constants by reversed-phase high-performance liquid chromatography, Journal of Medicinal Chemistry, vol.31, issue.10, pp.1923-1933, 1988.
DOI : 10.1021/jm00118a010

M. Pomper, H. Vanbrocklin, A. Thieme, R. Thomas, D. Kiesewetter et al., 11.beta.-Methoxy-, 11.beta.-ethyl, and 17.alpha.-ethynyl-substituted 16.alpha.-fluoroestradiols: receptor-based imaging agents with enhanced uptake efficiency and selectivity, Journal of Medicinal Chemistry, vol.33, issue.12, pp.3143-3155, 1990.
DOI : 10.1021/jm00174a009

D. 'amboise, M. Hanai, and T. , Hydrophobicity and Retention in Reversed Phase Liquid Chromatography, Journal of Liquid Chromatography, vol.14, issue.2, pp.229-244, 1982.
DOI : 10.1080/01483918208069068

F. Yang, . Li, . Ma, S. Bu, and . Zhang, Synthesis and characterization of fluorinated polyimides derived from novel unsymmetrical diamines, Journal of Fluorine Chemistry, vol.131, issue.7, pp.767-775, 2010.
DOI : 10.1016/j.jfluchem.2010.03.014

X. Bao, . Lu, . Liow, . Ss-zoghbi, . Jenko et al., F-Labeled Positron Emission Tomography (PET) Radioligand for Brain Histamine Subtype-3 Receptors Based on a Nonimidazole 2-Aminoethylbenzofuran Chemotype, Journal of Medicinal Chemistry, vol.55, issue.5, pp.2406-2415, 2012.
DOI : 10.1021/jm201690h

M. Görmen, . Pigeon, . Top, . Hillard, C. Huche et al., Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells, ChemMedChem, vol.693, issue.639, pp.2039-2050, 2010.
DOI : 10.1002/cmdc.201000286

V. Winkler, R. Ma-nyman, and . Egan, Diethylstilbestrol cis-trans isomerization and estrogen activity of diethylstilbestrol isomers, Steroids, vol.17, issue.1-5, pp.197-207, 1971.
DOI : 10.1016/S0039-128X(71)80124-1

. Bs-katzenellenbogen, . Norman, . Eckert, and . Sw-peltz, Bioactivities, estrogen-receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxytamoxifen isomers in MCF-7 human-breast cancer-cells, Cancer Res, vol.44, pp.112-119, 1984.

C. Osborne, . Coronado, . Dc-allred, M. Wiebe, and . Degregorio, Acquired Tamoxifen Resistance: Correlation With Reduced Breast Tumor Levels of Tamoxifen and Isomerization of Trans-4-Hydroxytamoxifen, JNCI Journal of the National Cancer Institute, vol.83, issue.20, pp.1477-1482, 1991.
DOI : 10.1093/jnci/83.20.1477

C. Osborne, . Vj-wiebe, D. R. Wl-mcguire, M. W. Ciocca, and . Degregorio, Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients., Journal of Clinical Oncology, vol.10, issue.2, pp.304-310, 1992.
DOI : 10.1200/JCO.1992.10.2.304

L. Gao, . Tu, . Wegman, L. Wingren, and . Eriksson, A Mechanistic Hypothesis for the Cytochrome P450-Catalyzed Cis???Trans Isomerization of 4-Hydroxytamoxifen: An Unusual Redox Reaction, Journal of Chemical Information and Modeling, vol.51, issue.9, pp.2293-2301, 2011.
DOI : 10.1021/ci2001082

M. Coogan, M. Dyson, and . Bochmann, Introduction to the Organometallics in Biology and Medicine Issue, Organometallics, vol.31, issue.16, pp.5671-5672
DOI : 10.1021/om300737y

G. Sava, . Jaouen, . Hillard, and . Bergamo, Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the future of metal-based anticancer drugs, Dalton Transactions, vol.15, issue.27, pp.8226-8234, 2012.
DOI : 10.1039/c2dt30075c

. Hz, 66 (s, 1H : y), 9.85 (s, 1H : p), 10.33 (s, 1H: z), 2H : m), 7.19 (d, J = 8.5 Hz, 2H : f), 7.25 (d, J = 8.5 Hz, 2H : g), 7.50 (d, J = 8.5 Hz 2H : r), 2.44-2.58 (q, 2H : b), 3.80 (t, J = 1.9 Hz, 2H : ?) : Cp), 4.23 (q, 2H : j) 2H : g), pp.44-46

. Hz, 66 (s, 1H : y), 9.88 (s, 1H : p), 10.33 (s, 1H : z)

?. Kbr, (C Ar - H stretch), 2931, 2866 (C Alk -H stretch), 1759 (OC=O stretch), 1655 (NC=O stretch, 1250 (C-O stretch). SM (ESI, pp.3244-3040

?. Kbr, 3055 (C Ar - H stretch), 2962, 2866 (C Alk -H stretch), pp.1508-1261

O. @bullet, (4-hydroxyphényl)-2-phénylbut-1-èn-1-yl]phényl}subéramide Une solution méthanolique de C-PhAm est versée dans une solution aqueuse concentrée de NaOH. Le mélange est mis sous agitation pendant une nuit à température ambiante. Puis, la solution est acidifiée à l'HCl et le produit est extrait à l'AcOEt. La phase organique est séchée sur MgSO 4 , filtrée et évaporée. Le brut de la réaction est purifié sur une colonne de gel de silice

. Hz, 2H : f), 6.68 (s, 1H : y'), 7.22 (s, 1H : y), 2H : n), 9.18 (s, 1H : i), 9.90 (s, 1H : p), p.4060

?. Kbr, 1264 (C-O stretch) SM (IC, Alk -H stretch), 1667 (NC=O stretch), 1595 (C Ar =C Ar stretch), pp.3308-3050, 2859.

J. Park and . Lee, Carbon-bridged ferrocenophanes In: Modern Cyclophane Chemistry, pp.131-157, 2004.

D. Plazuk, . Vessières, . Hillard, . Buriez, . Labbé et al., A [3]Ferrocenophane Polyphenol Showing a Remarkable Antiproliferative Activity on Breast and Prostate Cancer Cell Lines, Journal of Medicinal Chemistry, vol.52, issue.15, pp.4964-4967, 2009.
DOI : 10.1021/jm900297x
URL : https://hal.archives-ouvertes.fr/hal-00448988

M. Görmen, . Pigeon, . Top, M. Vessières, . Plamont et al., Facile synthesis and strong antiproliferative activity of disubstituted diphenylmethylidenyl-[3]ferrocenophanes on breast and prostate cancer cell lines, MedChemComm, vol.48, issue.639, pp.149-151, 2010.
DOI : 10.1039/c0md00026d

T. Turbitt and . Watts, Bridged ferrocenes, Journal of Organometallic Chemistry, vol.46, issue.1, pp.109-117, 1972.
DOI : 10.1016/S0022-328X(00)90481-9

O. Dogan, . Senol, . Zeytinci, . Koyuncu, and . Bulut, Efficient synthesis of ferrocenylenones by Friedel???Crafts acylation with EtAlCl2???Me3Al, Journal of Organometallic Chemistry, vol.690, issue.2, pp.430-434, 2005.
DOI : 10.1016/j.jorganchem.2004.09.055

M. Görmen, . Plazuk, . Pigeon, M. Hillard, . Plamont et al., Comparative toxicity of [3]ferrocenophane and ferrocene moieties on breast cancer cells, Tetrahedron Letters, vol.51, issue.1, pp.118-120, 2010.
DOI : 10.1016/j.tetlet.2009.10.102

2. Hz and J. =. , 1H : z), 2H : n), 7.38 (t, J = 7.2 Hz, 2H : g), 9.74 et 9.91 pour l'isomère E (s, 1H : p), p.97, 1930.

?. Kbr, 1701 (OC=O stretch), 1662 (NC=O stretch), 1593 (C Ar =C Ar stretch), 1520 (N-H bend) SM (IC, C Alk -H stretch) HPLC (R T, vol.3089, issue.2927, pp.3313-3051

?. Kbr, 1666 (NC=O stretch), 1593 (C Ar =C Ar stretch), 1520 (N-H bend) SM (IC, R F : (AcOEt): 0.92, pp.3321-3086

. Hz, 2H : b), 3.56 (s, 3H : z), 3.95 (t, J = 1.8 Hz, 2H : ?'), 4.01 (s, 4H : ? et ?), 2H : g), 9.76 et 9.93 pour E (s, 1H : p), pp.2726-2728

F. @bullet, {[3]ferrocénophan-1-ylidène(phényl)méthyl}phényl)subéramide Réactifs et conditions : FnTAM-OPOA (1 mmol, 0.56 g), THF (10 mL, ClCO 2 Et (2 mmol, 0.19 mL), Et 3 N (2.5 mmol, 0.35 mL), NaNH 2 (excès). Eluant pour la colonne : mélanges hexane/AcOEt. 36% (0.20 g) de produit est obtenu. Solide jaune. Z/E = 96

?. Kbr, 3093 (C Ar -H stretch), 2927, 2854 (C Alk -H stretch), 1662 (NC=O stretch), 1597 (C Ar =C Ar stretch), 1519 (N-H bend) SM (IC, pp.578-561

S. Cohen and S. Lippard, Cisplatin: From DNA damage to cancer chemotherapy, Prog Nucleic Acid Res Mol Biol, vol.67, pp.93-130, 2001.
DOI : 10.1016/S0079-6603(01)67026-0

S. Top, . Vessières, . Leclercq, . Quivy, . Tang et al., Synthesis, Biochemical Properties and Molecular Modelling Studies of Organometallic Specific Estrogen Receptor Modulators (SERMs), the Ferrocifens and Hydroxyferrocifens: Evidence for an Antiproliferative Effect of Hydroxyferrocifens on both Hormone-Dependent and Hormone-Independent Breast Cancer Cell Lines, Chemistry - A European Journal, vol.9, issue.21, pp.5223-5236, 2003.
DOI : 10.1002/chem.200305024

A. Vessières, . Top, . Pigeon, . Hillard, . Boubeker et al., Modification of the Estrogenic Properties of Diphenols by the Incorporation of Ferrocene. Generation of Antiproliferative Effects in Vitro, Journal of Medicinal Chemistry, vol.48, issue.12, pp.3997-3940, 2005.
DOI : 10.1021/jm050251o

W. Wlassoff, . Cd-albright, . Sivashinski, . Ivanova, R. Appelbaum et al., Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate, Journal of Pharmacy and Pharmacology, vol.41, issue.639, pp.1549-1553, 2007.
DOI : 10.1211/jpp.59.11.0013

E. Hillard, . Vessières, . Thouin, C. Jaouen, and . Amatore, Ferrocene-Mediated Proton-Coupled Electron Transfer in a Series of Ferrocifen-Type Breast-Cancer Drug Candidates, Angewandte Chemie International Edition, vol.44, issue.2, pp.285-290, 2006.
DOI : 10.1002/anie.200502925

E. Hillard, . Pigeon, C. Vessières, G. Amatore, and . Jaouen, The influence of phenolic hydroxy substitution on the electron transfer and anti-cancer properties of compounds based on the 2-ferrocenyl-1-phenyl-but-1-ene motif, Dalton Transactions, vol.5, issue.43, pp.5073-5081, 2007.
DOI : 10.1039/b705030e
URL : https://hal.archives-ouvertes.fr/hal-01230399

P. Pigeon, . Top, . Zekri, . Hillard, M. Vessières et al., 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, vol.694, issue.6, pp.895-901, 2009.
DOI : 10.1016/j.jorganchem.2008.11.035

O. Zekri, . Hillard, . Top, . Vessières, . Pigeon et al., Role of aromatic substituents on the antiproliferative effects of diphenyl ferrocenyl butane compounds, Dalton Trans, vol.22, pp.4318-4326, 2009.

O. Buriez, . Labbé, . Pigeon, C. Jaouen, and . Amatore, Electrochemical attachment of a conjugated amino???ferrocifen complex onto carbon and metal surfaces, Journal of Electroanalytical Chemistry, vol.619, issue.620, pp.169-175, 2008.
DOI : 10.1016/j.jelechem.2008.04.012
URL : https://hal.archives-ouvertes.fr/hal-01230398

W. Lai, J. Zahid, and . Uetrecht, Metabolism of trimethoprim to a reactive iminoquinone methide by activated human neutrophils and hepatic microsomes, J Pharm Exp Ther, vol.291, pp.292-299, 1999.

. Mc-damsten, . Jsb-de-vlieger, . Wma-niessen, N. Irth, . Vermeulen et al., Trimethoprim: Novel Reactive Intermediates and Bioactivation Pathways by Cytochrome P450s, Chemical Research in Toxicology, vol.21, issue.11, pp.2181-2187, 2008.
DOI : 10.1021/tx8002593

G. Bucher, A Laser Flash Photolysis Study on 2-Azido-N,N-diethylbenzylamine ??? The Reactivity of Iminoquinone Methides in Solution, European Journal of Organic Chemistry, vol.2001, issue.13, pp.2463-2475, 2001.
DOI : 10.1002/1099-0690(200107)2001:13<2463::AID-EJOC2463>3.0.CO;2-6

. Par, Schéma 3) ?qui a également révélé une activité antiproliférative contre les cellules MDA-MB-231? ne subit pas une séquence d'oxydation stimulée par une base dans les mêmes conditions que pour l'amine Fc-aline ou le diphénol Fc-diphol. Dès lors, nous avons proposé que le mécanisme d'activation redox pouvait se produire une fois que l'amide Fc-alide était convertie in vitro en l'amine Fc

. Schéma-3, Oxydation du 4-(2-ferrocényl-1-phénylbut-1-én-1-yl)acétanilide Fc-alide non observable et sa valeur d

K. Sakano, Y. Oikawa, S. Hiraku, and . Kawanishi, Mechanism of metal-mediated DNA damage induced by a metabolite of carcinogenic acetamide, Chemico-Biological Interactions, vol.149, issue.1, pp.51-59, 2004.
DOI : 10.1016/j.cbi.2004.06.005

D. Plazuk, . Vessieres, . Hillard, . Buriez, . Labbé et al., A [3]Ferrocenophane Polyphenol Showing a Remarkable Antiproliferative Activity on Breast and Prostate Cancer Cell Lines, Journal of Medicinal Chemistry, vol.52, issue.15, pp.4964-4967, 2009.
DOI : 10.1021/jm900297x
URL : https://hal.archives-ouvertes.fr/hal-00448988

M. Görmen, . Pigeon, . Top, . Hillard, C. Huché et al., Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells, ChemMedChem, vol.693, issue.639, pp.2039-2050, 2010.
DOI : 10.1002/cmdc.201000286

. Synthèse-de-diamides-fn-dibut, N. Fn-dihex-et-fn-dioct-les, and N. , -[([3]ferrocénophan-1-ylidèneméthylene)bis(4,1-phénylène)]dialkanamides dérivés de la dianiline Fn-dialine et les chlorures de butyryle (bu), hexanoyle (he) et octanoyle (oc) peuvent être préparés selon deux voies. La voie-A implique, dans un premier temps, la réaction d'amidation de la 4,4'-diaminobenzophénone avec les chlorures d'acyle correspondants en présence de la triéthylamine Les produits sont obtenus avec d'excellents rendements

. Dans-un-deuxième-temps, une réaction d'hétérocouplage entre la [3]ferrocénophan-1- one et les N,N'-[carbonylbis(4,1-phénylène)]dialkanamides formés préalablement a été réalisée (Schéma 6) Les produits ont été obtenus avec des rendements supérieurs à ceux que l'on attendrait pour une réaction d

. De-la-même-manière, les analogues tétraméthylés des deux anilines primaires : (i) l'organique Ph-dialine et (ii) l'inexistante organométallique 4,4'-(2-ferrocénylbut-1-éne-1,1- diyl)dianiline ont été aussi préparés. Ainsi, la propiophénone et le propionylferrocène ont réagi indépendamment avec la cétone de Michler selon la réaction de McMurry

P. Messina, . Labbé, . Buriez, . Hillard, D. Vessières et al., Deciphering the Activation Sequence of Ferrociphenol Anticancer Drug Candidates, Chemistry - A European Journal, vol.28, issue.21, pp.6581-6587, 2012.
DOI : 10.1002/chem.201103378

Y. Tan, . Pigeon, . Top, . Labbé, . Buriez et al., Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells, Dalton Transactions, vol.46, issue.639, pp.7537-7549, 2012.
DOI : 10.1002/chem.201103378
URL : https://hal.archives-ouvertes.fr/hal-01230385

L. Voltammogrames-ont-Été-enregistrés-d, une solution 0.5 mM d'analyte dans une solution 0.1 M de Bu 4 NBF 4 dans le MeOH Électrode de travail : Pt (? = 0.5 mm), électrode auxiliaire : baguette d'acière inoxydable

@. N. Fn-dibut, 1-phénylène)]dibutyramide Réactifs et quantités : Fn-dialine (2.36 mmol, 0.99 g) Eluant pour la colonne: CHCl 3 /AcOEt/AcOH: 2/1/1. La première fraction a été identifié comme le produit désiré, la deuxième était le produit de monoamidation et la troisième

. Hz, 1H : i), 2H : l'), 2.27 (t, J = 7.4 Hz, 2H : k), 2.35 (t, J = 7.4 Hz, 2H : k'), pp.9632-9634

?. Kbr, 1662 (N=CO stretch), 1597 (C Ar =C Ar stretch) 1523 (N-H bend), 1400 (C-N stretch) SM (IC, Macherey-Nagel C18, MeOH). pf, pp.3298-3101

B. Voie, . Réactifs, and . Quantités, Fn-dialine (0.59 mmol, 0.25 g) THF (15 mL), chlorure d'octanoyle (1.18 mmol, 0.2 mL) Et 3 N (1.43 mmol, 0.2 mL) Éluant pour la colonne: CHCl 3 /AcOEt /AcOH: 2/1/1. La première fraction est le produit désiré, la seconde est le produit de monoamidation et la troisième

3. Hz, 3H : q), 1.21-1.45 (m, 16H : p', p, o', o, n', n, m' et m), 1.55-1.78 (m, 4H : l' et l), '), 2.37 (t, J = 7.4 Hz, 2H : k) 2H : ?), p.88299802

2. Hz, 1H : i), pp.98-107

?. Kbr, 3101 (C Ar -H stretch), 2924, 2854 (C Alk -H stretch), 1662 (NC=O stretch, 1400 (C-N stretch). SM (IC Calc. pour C 42 H 52 FeN 2 O 2 (%): C, 74.99; H, pp.3298-1597

@. N. Fn-dihex, 1-phénylène)]dihexanamide Réactifs and quantités: Zn (24 mmol, 1.57 g) TiCl 4 (12 mmol, 1.3 mL), THF (30 mL), dihex (2.4 mmol, 0.98 g), Fn-dialine (2.4 mmol, 0.58 g), THF (20 mL) Le mélange est agité pendant 15 min après l'addition des cétones

I. Kbr, (C Ar -H stretch), 2927, 2858 (C Alk -H stretch), 1662 (NC=O stretch, 1400 (C-N stretch). SM (IC, pp.3298-3043

. Anal and . Calc, C, 74.02; H, 7.19; N, 4.54. Trouvé : C, 73, Macherey-Nagel, C18, 5 µm, 4.6 x 250 mm, MeOH, pp.38-44

@. Ph-dialine, -phénylbut-1-éne-1,1-diyl)dianiline Réactifs et quantités : Zn (48 mmol, 3.14 g), TiCl 4 (24 mmol, 2.6 mL), THF (80 mL)

. Propiophénone, 78 mmol, 0.91 g), 4,4'-diaminobenzophénone (5.09 mmol, 1.08 g), THF (40 mL), DMSO (1 mL) Temps de réaction : 5 min

?. Kbr, (C Alk -H stretch), 1616 (NH 2 scissoring), 1508 (C Ar =C Ar stretch), 1280 (C Ar -N stretch) MS (IC, pp.3432-3024, 2870.

@. Ph-dialinetm, -phénylbut-1-éne-1,1-diyl)bis(N

Q. Réactifs, Zn (72 mmol, 4.71 g), TiCl 4 (36 mmol, 3.9 mL), THF (100 mL)

. Propiophénone, 6 mmol, 1.02 g), bis[(4-(diméthylamino)phényl]méthanone (7.6 mmol, 2.04 g), THF (60 mL) Temps de réaction : 20 min

?. Kbr, 2962, 2877 (C Alk -H stretch), 1608, 1515 (C Ar =C Ar stretch), 1342 (C Ar -N stretch) SM (IE, pp.370-373

Q. Réactifs, Zn (72 mmol, 4.71 g) TiCl 4 (36 mmol, 3.9 mL), THF (100 mL), bis

C. Au-comportement-dans-l-'acétone and D. Dans-le, Spectre 2) nous n'avons pas observé de changements notables