Résultat de la recherche
Arene ruthenium and pentamethylcyclopentadienyl rhodium and iridium complexes containing N,O-chelating ligands derived from piroxicam: Synthesis, molecular structure and cytotoxicity
The non-steroidal anti-inflammatory and anti-arthritic drug piroxicam (LH) reacts with arene ruthenium dichloride dimers in refluxing dichloromethane to give the complexes [(?6-arene)Ru(?2-N,O-L)Cl] (3: arene = C6H5Me, 4: arene = p-MeC6H4Pri, 5: arene = C6Me6). The reaction seems to proceed via the intermediates [(?6-arene)Ru(N-LH)Cl2], which can be obsd. for arene = C6H5Me (1) and isolated in the case of arene = p-MeC6H4Pri (2). The analogous reaction with pentamethylcyclopentadienyl rhodium and iridium gives the complexes [(?5-C5Me5)M(?2-N,O-L)Cl] (6: M = Rh, 7: M = Ir). The single-crystal x-ray structure analyses of the p-cymene ruthenium derivs. 4 and 2 show the metal atom in the archetypical piano stool geometry; in 4 the piroxicamato ligand is coordinated in a bidentate fashion through the pyridine nitrogen atom and the enolic oxygen atom, while in 2 the intact piroxicam ligand is coordinated in a monodentate fashion through the pyridine nitrogen atom. The piroxicamato complexes 3-5 are weakly cytotoxic towards human ovarian cancer cells. [on SciFinder(R)]
Arene ruthenium dichloro complexes containing isonicotinic ester ligands: Synthesis, molecular structure and cytotoxicity
A series of p-cymene ruthenium dichloro complexes contg. isonicotinic ester ligands, [(arene)RuCl2NC5H4-4-COO-C6H4-p-O-(CH2)n-CH3] (n = 1: 1, n = 3: 2, n = 5: 3, n = 7: 4, n = 9: 5, n = 11: 6, n = 13: 7, n = 15: 8), were prepd. from p-cymene ruthenium dichloro dimer and the corresponding isonicotinic ester ligand. The single-crystal x-ray anal. of 1 shows the mol. to adopt the usual pseudo-tetrahedral piano-stool geometry, the isonicotinic ester ligand being coordinated through the nitrogen atom. The cytotoxicity of all complexes and of the free ligands was studied towards human ovarian cancer cells; high activities were obsd. only for n = 9 (presenting a chain with ten carbon atoms), both as far as the free ligands and the complexes are concerned. Based on this result, a new isonicotinic ester ligand with a C10 substituent contg. a terminal alc. function, NC5H4-4-COO-C6H4-p-O-(CH2)10-OH, was synthesized by a four-step method, and arene ruthenium complexes thereof, [(arene)RuCl2NC5H4-4-COO-C6H4-p-O-(CH2)10-OH] (arene = C6H6: 9a, arene = p-MeC6H4Pri: 9b, arene = C6Me6: 9c) were prepd. The complexes 9a and 9b show indeed remarkable anticancer activities, the IC50 values for human ovarian cancer cells being in the submicromolar range. The highest cytotoxicity was obsd. for complex 9b, with IC50 values of 0.18 ?M for A2780 and 3.04 ?M for the cisplatin-resistant mutant A2780cisR. [on SciFinder(R)]
Thiolato-Bridged Arene-Ruthenium Complexes: Synthesis, Molecular Structure, Reactivity, and Anticancer Activity of the Dinuclear Complexes [(arene)2Ru2(SR)2Cl2]
Treatment of an arene-Ru dichloride dimer with thiols RSH to lead to cationic trithiolato complexes [(arene)2Ru2(SR)3]+ proceeds through the neutral thiolato complexes [(arene)2Ru2(SR)2Cl2], which were isolated and characterized for arene = p-MeC6H4CHMe2 and R = CH2Ph (1), CH2CH2Ph (2), CH2C6H4CMe3 (3), and C6H11 (4). The single-crystal x-ray structure anal. of the p-tert-butylbenzyl deriv. 3 reveals that the two Ru atoms are bridged by the two thiolato ligands without a metal-metal bond. The neutral dithiolato complexes[(arene)2Ru2(SR)2Cl2] (1-3) are intermediates in the formation of the cationic trithiolato complexes [(arene)2Ru2(SR)3]+ (5-7). Of the new [(arene)2Ru2(SR)2Cl2] complexes, deriv. 2 is highly cytotoxic against human ovarian cancer cells, with IC50 values of 0.20 ? for the A2780 cell line and 0.31 for the cisplatin-resistant cell line A2780cisR. [on SciFinder(R)]
Synthesis and Anticancer Activity of Long-Chain Isonicotinic Ester Ligand-Containing Arene Ruthenium Complexes and Nanoparticles
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).
Synthesis, characterisation and in vitro anticancer activity of hexanuclear thiolato-bridged arene ruthenium metalla-prisms
Hexanuclear hexacationic thiolato-bridged arene ruthenium metalla-prisms of the general formula [[(?6-p-cymene)Ru]6(?-SR)6(?3-tpt)2][OTf]6 (R = CH2Ph, CH2C6H4-p-tBu, CH2CH2Ph; tpt = 2,4,6-tri-4-pyridyl-1,3,5-triazine), obtained from the self-assembly of dinuclear precursors [(p-cymene)2Ru2(?-SR)2Cl2] with tpt and AgCF3SO3, have been isolated and fully characterized as triflate salts. The metalla-prisms are highly cytotoxic against human ovarian cancer cells, esp. towards the cisplatin-resistant cell line A2780cisR (IC50
Thiolato-Bridged Arene–Ruthenium Complexes: Synthesis, Molecular Structure, Reactivity, and Anticancer Activity of the Dinuclear Complexes [(arene)2Ru2 (SR)2Cl2]
Treatment of an arene–ruthenium dichloride dimer with thiols RSH to lead to cationic trithiolato complexes of the type [(arene) 2Ru2(SR)3]+ was shown to proceed through the neutral thiolato complexes [(arene)2Ru2(SR)2Cl2], which have been isolated and characterized for arene = p-MeC6H4iPr and R = CH2Ph (1), CH2CH2Ph (2), CH2C6H4-p-tBu (3), and C6H11 (4). The single-crystal X-ray structure analysis of the p-tert-butylbenzyl derivative 3 reveals that the two ruthenium atoms are bridged by the two thiolato ligands without a metal–metal bond. The neutral dithiolato complexes[(arene)2Ru2(SR)2Cl2] (1–3) are intermediates in the formation of the cationic trithiolato complexes [(arene)2Ru2(SR)3]+ (5–7). Of the new [(arene)2Ru2(SR)2Cl2] complexes, derivative 2 is highly cytotoxic against human ovarian cancer cells, with IC50 values of 0.20 μM for the A2780 cell line and 0.31 for the cisplatin-resistant cell line A2780cisR.
Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes
Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III) complexes (C5Me5)2Rh2(?-SR)2Cl2 (R = CH2Ph, 1; R = CH2CH2Ph, 2) and cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes [(C5Me5)2M2(?-SR)3]+ (M = Rh, R = CH2Ph, 3; M = Rh, R = CH2CH2Ph, 5; M = Rh, R = CH2C6H4-p-tBu, 7: M = Ir, R = CH2Ph, 4; M = Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-tBu, 8) were synthesized from the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers (C5Me5)2M2(?-Cl)2Cl2 by reaction with the corresponding thiol deriv. (RSH). Complexes 3-8 were isolated as chloride salts. All complexes were obtained in good yield and were fully characterized by spectroscopic methods. The mol. structures of the neutral complexes (1 and 2) show interesting features: the two Rh atoms are bridged by two thiolato ligands with no metal-metal bonds and the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each other, an uncommon conformation for such dinuclear complexes. These structural features were rationalized using DFT calcns. Addnl., the antiproliferative activity of the complexes was evaluated against the cancerous A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian cell lines and on the noncancerous HEK293 human embryonic kidney cells. All complexes are active and the cationic Ir complexes 4, 6 and 8 are particularly cytotoxic, with IC50 values in the nanomolar range (IC50 < 0.1 ?M). The catalytic activity of the complexes for the oxidn. of glutathione (GSH) to GSSG was evaluated by NMR spectroscopy. [on SciFinder(R)]
Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(?6-p-MeC6H4Pri)2Ru2(SC6H4-p-X)3]+: synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential
A series of cationic binuclear areneruthenium tris(arenethiolato)-bridged complexes [(?6-p-cymene)2Ru2(?-SC6H4-p-X)3]+ (1-11; X = H, Me, Ph, Br, OH, NO2, OMe, CF3, F, iPr, tBu) were prepd. by complexation of the chloride-bridged dimer [(?6-p-cymene)2Ru2(?-Cl)2Cl2] with the corresponding thiols, isolated as the chloride salts, and further studied for their electrochem. properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidn. Complex 1 was also compared with the benzene and hexamethylbenzene analogs [(?6-C6H6)2Ru2(?-SC6H5)3]+ (12) and [(?6-C6Me6)2Ru2(?-SC6H5)3]+ (13). The most active compd. [11]Cl was structurally studied by single-crystal x-ray diffraction anal. The concns. corresponding to 50% inhibition of cancer cell growth (IC50 values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC50 value of 0.03 ?M in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidn. of GSH, although there is no clear correlation between the IC50 values and the turnover frequencies at about 50% conversion. However, the cytotoxicity is tentatively correlated to the physicochem. properties of the compds. detd. by the electronic influence of the substituents X (Hammett consts. ?p) and the lipophilicity of the thiols p-XC6H4SH (calcd. log P parameters). [on SciFinder(R)]