[Show abstract][Hide abstract] ABSTRACT: A series of seven new ruthenium(II)–arene complexes of general formula [Ru(η6-p-cymene)(L1−7)Cl], where L1−7 are fluoro, chloro, bromo or methyl derivatives of picolinic acid or isoquinoline-3-carboxylic acid has been synthesized and characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy and ESI mass spectrometry. X-ray diffraction studies of two compounds showed the usual piano-stool geometry, with coordination of picolinato ligands through the pyridine nitrogen and the carboxylic group oxygen atom (N/COO− donor set). Cytotoxicity of complexes in vitro has been evaluated in three human tumor cell lines: cervix carcinoma (HeLa), melanoma (FemX), lung adenocarcinoma (A549) and one normal cell line (MRC-5). Complex with isoqinoline-3-carboxylic acid as ligand, exhibited significantly lower cytotoxic activity in normal cells (MRC-5) against high activity observed in panel of tumor cells and prominent cell type selectivity among tumor cells.
Journal of Organometallic Chemistry 01/2014; 749:343-349. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our previous study, ruthenium(II)-p-cymene complexes of general formula [(η(6)-p-cymene)Ru(L)Cl2], L: 3-acetylpyridine (1), 2-amino-5-chloropyridine (2); and [(η(6)-p-cymene)Ru(HL)Cl], HL: 2,3-pyridinedicarboxylic acid (3), 2,4-pyridinedicarboxylic acid (4), revealed low antiproliferative activity, except complex [(η(6)-p-cymene)RuCl(picolinic acid)]·H(2)O (5) which exhibited IC(50) around 80 μM. In this study we further investigated in vitro potential of antimetastatic action of ruthenium complexes on HeLa and two endothelial cell lines. Comparison of structure and activity of five complexes indicated heterogenic mode of activity, with regard to the potential of antimetastatic and antiproliferative effect. Replacement of substituted pyridine ligand with picolinic acid (complex 5) around Ru(II) center contributed to complex cytotoxicity and ruthenium DNA binding affinity. Analysis of ruthenium(II) accumulation in DNA and protein fractions of HeLa cells, using ICP-OES revealed significantly higher content of complex 5 in DNA fraction in comparison to the other tested compounds. It also altered cell cycle progression, affected expression of DNA repair enzymes ERCC1 and MSH2, and showed enhanced activity in combination with 3-aminobenzamide. Regardless of their effect on cell growth, Ru(II) complexes exerted antimetastatic effect on several tumor cell lines in vitro, achieved mostly by the effect on cell adhesion, migration and angiogenesis, while picolinate ruthenium(II)-arene additionally exerted inhibitory effect on extracellular matrix degradation.
Journal of inorganic biochemistry 12/2011; 108:53-61. · 3.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A ruthenium(II)–arene complex with picolinic acid, [(η 6 -p-cyme-ne)RuCl(pico)]·H 2 O, was prepared by the reaction of [(η 6 -p-cymene)RuCl 2 ] 2 with picolinic acid in a 1:2 molar ratio in 2-propanol. The compound was cha-racterized by elemental analysis, and IR and NMR spectroscopy. X-ray diffrac-tion analysis showed that the molecule adopts a "three-leg piano-stool" geo-metry, which is common for this type of complexes. The cytotoxic activity of the complex was tested in two human cancer cell lines HeLa (cervix) and FemX (melanoma) by MTT assay. The IC 50 values were at 82.0 and 36.2 µmol dm -3 for HeLa and FemX cells, respectively.
[Show abstract][Hide abstract] ABSTRACT: Ruthenium(II)-arene complexes of general formulae [(eta(6)-p-cymene)Ru(L(1-3))Cl(2)], where L(1-3) is 3-acetylpyridine (1), 4-acetylpyridine (2) and 2-amino-5-chloropyridine (3), correspondingly, [(eta(6)-p-cymene)Ru(HL(4,5))Cl(2)], where HL(4) and HL(5) are respectively isonicotinic acid (4) and nicotinic acid (5) and [(eta(6)-p-cymene)Ru(HL(6-9))Cl], where H(2)L(6-9) represent 2,3-pyridinedicarboxylic acid (6), 2,4-pyridinedicarboxylic acid (7), 2,5-pyridinedicarboxylic acid (8) and 2,6-pyridinedicarboxylic acid (9), were prepared by the reaction of [(eta(6)-p-cymene)(2)RuCl(2)](2) (10) with the corresponding ligand in 1:2 molar ratio in isopropanol. The complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies. According to these data the molecules adopt the usual "three-leg piano-stool" geometry which is common for this type of complexes. The structures of 1 and 7 were determined by X-ray crystallography. The complexes revealed low antiproliferative activity in six investigated tumor cell lines (HeLa, B16, FemX, MDA-MB-361, MDA-MB-453 and LS-174). The reaction of 6 with 9-methyladenine was studied by (1)H NMR, (1)H, (1)H COSY and (1)H, (1)H NOESY spectroscopy.
European Journal of Medicinal Chemistry 03/2010; 45(3):1051-8. · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metal semicarbazone and thiosemicarbazone complexes have attracted much attention due to their diverse biological activities. Because of the ability of ruthenium(II)-arene species to coordinate to different classes of ligands, they are suitable for fine-tuning chemical and pharmaceutical properties. Ruthenium(II) arene-complexes containing different types of ligands: namely caprylic hydrazide (a hydrazide with a long hydrocarbon chain), isonicotinic acid hydrazide (a hydrazide with an aromatic pyridine ring), thiosemicarbazones and semicarbazones (derived from the reaction of 3- and 4-acetylpyridine with either thiosemicarbazide or caprylic hydrazide), were obtained in the reaction of [(η6-p-cymene)RuCl2]2 with the corresponding ligands in a 1:2 or 1:2.2 molar ratio in methanol, ethanol or isopropanol with mild heating. The complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies. The structure of complex 1 was determined by X-ray crystallography. Antiproliferative activity of the investigated complexes, determined for three human cancer cell lines (HeLa, A549 and LS-174) revealed moderate activity without significant influence on the matrix metalloproteinases (MMP-2 and MMP-9) activity.
[Show abstract][Hide abstract] ABSTRACT: Acid–base equilibria of the aqua adducts of Ru(II) arene complexes, general formulae [(η6-p-cymene)Ru (L1−3)Cl2] where L1 = 3-acetylpyridine (1), L2 = 4-acetylpyridine (2) and L3 = 2-amino-5-chloropyridine (3), then [(η6-p-cymene)Ru(HL4)Cl2] with HL4 = isonicotinic acid (4); [(η6-p-cymene)Ru(HL5−8)Cl] where H2L5 = 2,3-pyridine dicarboxylic acid (5), H2L6 = 2,4-pyridine dicarboxylic acid (6), H2L7 = 2,5-pyridine dicarboxylic acid (7) and H2L8 = 2,6-pyridine dicarboxylic acid (8) have been studied. pK
a values were determined by potentiometry at 25 °C and constant ionic strength of 0.1 M NaNO3. The assumed equilibria were confirmed by UV and 1H-NMR spectroscopy.
Journal of the Iranian Chemical Society 9(1). · 1.47 Impact Factor