Voici les éléments 1 - 7 sur 7
  • Publication
    Accès libre
    Organometallic Cages as Vehicles for Intracellular Release of Photosensitizers
    (2012)
    Schmitt, Frédéric
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    ;
    Barry, Nicolas P.E.
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    Juillerat-Jeanneret, Lucienne
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    ;
    Water-soluble metalla-cages were used to deliver hydrophobic porphin molecules to cancer cells. After internalization, the photosensitizer was photoactivated, significantly increasing the cytotoxicity in cells. During the transport, the photosensitizer remains nonreactive to light, offering a new strategy to tackle overall photosensitization, a limitation often encountered in photodynamic therapy.
  • Publication
    Accès libre
    Synthesis and Anticancer Activity of Long-Chain Isonicotinic Ester Ligand-Containing Arene Ruthenium Complexes and Nanoparticles
    (2010) ;
    Khan, Farooq-Ahmad
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    Juillerat-Jeanneret, Lucienne
    ;
    Dyson, Paul J.
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    Renfrew, Anna K.
    Arene ruthenium complexes containing long-chain N-ligands L1 = NC5H4–4-COO–C6H4–4-O–(CH2)9–CH3 or L2 = NC5H4–4-COO–(CH2)10–O–C6H4–4-COO–C6H4–4-C6H4–4-CN derived from isonicotinic acid, of the type [(arene)Ru(L)Cl2] (arene = C6H6, L = L1: 1; arene = p-MeC6H4Pr i , L = L1: 2; arene = C6Me6, L = L1: 3; arene = C6H6, L = L2: 4; arene = p-MeC6H4Pr i , L = L2: 5; arene = C6Me6, L = L2: 6) have been synthesized from the corresponding [(arene)RuCl2]2 precursor with the long-chain N-ligand L in dichloromethane. Ruthenium nanoparticles stabilized by L1 have been prepared by the solvent-free reduction of 1 with hydrogen or by reducing [(arene)Ru(H2O)3]SO4 in ethanol in the presence of L1 with hydrogen. These complexes and nanoparticles show a high anticancer activity towards human ovarian cell lines, the highest cytotoxicity being obtained for complex 2 (IC50 = 2 μM for A2780 and 7 μM for A2780cisR).
  • Publication
    Accès libre
    Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy
    (2009)
    Schmitt, Frédéric
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    Govindaswamy, Padavattan
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    Zava, Olivier
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    Juillerat-Jeanneret, Lucienne
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    Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20-triphenylporphyrin as well as tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene ruthenium(II) derivatives (arene is C6H5Me or p-PriC6H4Me) were prepared and evaluated as potential dual photosensitizers and chemotherapeutics in human Me300 melanoma cells. In the absence of light, all tetranuclear complexes were cytotoxic (IC50 ≤ 20 μM), while the mononuclear derivatives were not (IC50 ≥ 100 μM). Kinetic studies of tritiated thymidine and tritiated leucine incorporations in cells exposed to a low concentration (5 μM) of tetranuclear p-cymene derivatives demonstrated a rapid inhibition of DNA synthesis, while protein synthesis was inhibited only later, suggesting arene ruthenium–DNA interactions as the initial cytotoxic process. All complexes exhibited phototoxicities toward melanoma cells when exposed to laser light of 652 nm. At low concentration (5 μM), LD50 of the mononuclear derivatives was between 5 and 10 J/cm2, while for the tetranuclear derivatives LD50 was approximately 2.5 J/cm2 for the [Ru46-arene)4 (tetra-4-pp)Cl8] complexes and less than 0.5 J/cm2 for the [Ru46-arene)4 (tetra-3-pp)Cl8] complexes. Examination of cells under a fluorescence microscope revealed the [Ru46-arene)4 (tetra-4-pp)Cl8] complexes as cytoplasmic aggregates, whereas the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes were homogenously dispersed in the cytoplasm. Thus, these complexes present a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizer.
  • Publication
    Accès libre
    Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells
    (2009)
    Schmitt, Frédéric
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    Auzias, Mathieu
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    Štěpnička, Petr
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    Sei, Yoshihisa
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    Yamaguchi, Kentaro
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    ; ;
    Juillerat-Jeanneret, Lucienne
    Diruthenium tetracarbonyl complexes of the type [Ru2 (CO)422-O2CR)2L2] containing a Ru–Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1–3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.
  • Publication
    Accès libre
    Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells
    (2009)
    Schmitt, Frederic
    ;
    Auzias, Mathieu
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    Stepnicka, Petr
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    Sei, Yoshihisa
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    Yamaguchi, Kentaro
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    ; ;
    Juillerat-Jeanneret, Lucienne
    Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(?2-?2-O2CR)2L2] contg. a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compds. 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compds. were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compds. demonstrated no cytotoxicity in the absence of laser irradn. but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compd. present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers. [on SciFinder(R)]
  • Publication
    Métadonnées seulement
    Ruthenium Porphyrin Compounds for Photodynamic Therapy of Cancer
    (2008)
    Schmitt, Frederic
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    Govindaswamy, Padavattan
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    Ang, Wee Han
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    Dyson, Paul J.
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    Juillerat-Jeanneret, Lucienne
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    Five 5,10,15,20-tetra(4-pyridyl)porphyrin (TPP) areneruthenium(II) derivs., a p-cymeneosmium, a pentamethylcyclopentadienyliridium and a pentamethylcyclopentadienylrhodium analog were prepd. and characterized as potential photosensitizing chemotherapeutic agents. The dinuclear areneruthenium complexes [Ru(?6-arene)(?-Cl)Cl]2 (arene = C6H6, C6H5CH3, p-iPrC6H4Me, C6Me6, and 1,4-C6H4(COOEt)2) react with TPP in MeOH to give the corresponding tetranuclear complexes [Ru4(?6-arene)4(TPP)Cl8] (arene = C6H6 (1, 56% yield), C6H5CH3 (2, 70%), p-iPrC6H4Me (3, 70%), C6Me6 (4, 79%), 1,4-C6H4(COOEt)2 (5, 73%)). The dinuclear p-cymeneosmium complex [Os(?6-p-iPrC6H4Me)(?-Cl)Cl]2 reacts with TPP to form the tetranuclear areneosmium complex [Os4(?6-p-iPrC6H4Me)4(TPP)Cl8] (6) in 47% yield. The isoelectronic Rh and Ir pentamethylcyclopentadienyl derivs. [Rh4(?5-C3Me5)4(TPP)Cl8] (7, 73%) and [Ir4(?5-C3Me5)4(TPP)Cl8] (8, 83%) were obtained in MeOH from the reaction of [M(?5-C5Me5)(?-Cl)Cl]2 (M = Rh, Ir) with TPP. The mol. structures of 4 and 7 were detd. by x-ray crystallog. The biol. effects of all these derivs. were assessed on human melanoma tumor cells, and their cellular uptake and intracellular localization were detd. All mols., except the Rh complex which was not cytotoxic, demonstrated comparable cytotoxicity in the absence of laser irradn. The Ru complexes exhibited excellent phototoxicities toward melanoma cells when exposed to laser light at 652 nm. Cellular uptake and localization microscopy studies of [Ru4(?6-C6H5CH3)4(TPP)Cl8] and [Rh4(?5-C5Me5)4(TPP)Cl8] revealed that they accumulated in the melanoma cell cytoplasm in granular structures different from lysosomes. The fluorescent porphyrin moiety and the metal component were localized in similar structures within the cells. Thus, the porphyrin areneruthenium(II) derivs. represent a promising new class of organometallic photosensitizers able to combine chemotherapeutic activity with photodynamic therapeutic treatment of cancer. [on SciFinder(R)]
  • Publication
    Accès libre
    Remarkable Anticancer Activity of Triruthenium-Arene Clusters Compared to Tetraruthenium-Arene Clusters
    (2007) ;
    Ang, Wee Han
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    Chérioux, Frédéric
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    Vieille-Petit, Ludovic
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    Juillerat-Jeanneret, Lucienne
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    ;
    Dyson, Paul J.
    The in vitro activity of a series of ruthenium clusters, [(η6-C6H6)(η6-C6Me6)2Ru3 (μ-H)3 (μ3-O)][BF4], [(η6-C6H6)(η6-1,4-iPrC6H4Me)(η6-C6Me6)Ru3 (μ-H)3 (μ3-O)][BF4], [(η6-C6H6)4Ru4 (μ-H)4][BF4]2, [(η6-C6H5Me)4Ru4 (μ-H)4][BF4]2 and [(η6-C6H6)4Ru4 (μ-H)3 (μ-OH)][Cl]2, has been evaluated against A2780 and A2780cisR ovarian carcinoma cell lines. Both triruthenium clusters are very active compared to ruthenium compounds in general, whereas the tetraruthenium clusters do not display significant cytotoxicities. Since the triruthenium clusters are known to form supramolecular interactions with arenes and other functions, it is possible that such interactions are also important with respect to their mode of biological activity. The X-ray structure analysis of [(η6-C6H5Me)4Ru4 (μ-H)4][PF6]2 is also reported.