Alexandra Karaliota

Novel copper(II) complex of N-propyl-norfloxacin and 1,10-phenanthroline with enhanced antileukemic and DNA nuclease activities.

We have synthesized and characterized a novel copper(II) complex of the fluoroquinolone antibacterial drug N-propyl-norfloxacin (Hpr-norf) in the presence of 1,10-phenanthroline (Phen) and studied its biological properties as antitumor antibiotic and antimicrobial agent. Human acute myeloid leukemia cell line HL-60, MTT assay, and Trypan blue assay were used to test the antileukemic, the cell viability, and the structural integrity of the cell membrane and cell proliferation properties of (chloro)(Phen)( N-propyl-norfloxacinato)copper(II) (complex 1), respectively. We found that the proliferation rate and viability of HL-60 cells decreased after treatment with complex 1, leading to cell death through apoptosis in a time-dependent manner. The antimicrobial activity of complex 1 has been tested, revealing an increased potency in comparison to the free Hpr-norf. Complex 1 proved to be capable of acting as an independent nuclease by inducing nicking of supercoiled pUC19 plasmid. Our results suggest that 1 may provide a valuable tool in cancer chemotherapy.

Metal complexes of the third-generation quinolone antimicrobial drug sparfloxacin: Structure and biological evaluation

Five metal complexes of the third-generation quinolone antimicrobial agent sparfloxacin with Fe(3+), VO(2+), Mn(2+), Ni(2+) and UO(2)(2+) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, sparfloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylate oxygen. The complexes are six-coordinate with distorted octahedral geometry. For VO(sparfloxacinato)(2)(H(2)O) the axial position, trans to the vanadyl oxygen, is occupied by a ketone oxygen atom. Molecular mechanics calculations have been performed in order to propose a model for the structure of each complex. The antimicrobial activity of the complexes has been tested against three microorganisms showing that they exhibit lower activity than free sparfloxacin. UV spectroscopic titration with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and the binding constants to CT DNA have been calculated. The cyclic voltammograms of the complexes in the presence of CT DNA have shown that they bind to CT DNA probably by the intercalative binding mode. Fluorescence competitive studies with ethidium bromide (EB) have revealed the ability of the complexes to displace the DNA-bound EB. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values.

Synthesis and characterization of a binuclear coumarin-3-carboxylate copper(II) complex

The copper(II) complex of coumarin-3-carboxylic acid (CcaH) has been prepared and characterized on the basis of elemental and thermal analysis, IR, Raman, EPR, UV-Vis reflectance and 1H-NMR spectra. A detail analysis of all spectra data is presented with particular emphasis on the elucidation of the coordination mode of the ligand and the structure of the complex. All data are consistent with a binuclear structure for the complex with four coumarin-3-carboxylates as bridges and one water ligand per copper ion. The significantly lower than the spin-only value magnetic moment of the complex and the EPR spectra at various temperature are indicative of a magnetic interaction between the two copper atoms.

Structure, antimicrobial activity and DNA-binding properties of the cobalt(II)-sparfloxacin complex.

The neutral mononuclear cobalt(II) complex with sparfloxacin has been prepared and characterized with physicochemical, spectroscopic and electrochemical techniques, and molecular mechanics calculations. The interaction of the complex with calf-thymus DNA has been investigated with UV spectroscopy, cyclic voltammetry, and competitive studies with ethidium bromide. The antimicrobial activity of the complex has been tested against three microorganisms.

Preparation and characterization of the seven coordinate cadmium(II) complex [Cd(3,4-H2dhb)2(H2O)3] · HCl · (3,4-H3dhb) · 2.5H2O; the first structural determination of a complex containing the 3,4-dihydroxybenzoato(−1)(3,4-H2dhb−) ligand

Abstract The 1:2:1 reaction of CdCl2·2.5H2O with 3,4-dihydroxybenzoic acid (3,4-H3dhb) and KOH in PrnOHH2O gave the unique, seven-coordinate cadmium(II) complex [Cd(3,4-H2dhb)2(H2O)3]·HCl·(3,4-H3dhb)·2.5H2O as one of the products. Crystal structure and 13Cd NMR studies showed that 3,4-H2dhb− behaves as a bidentate chelate with ligated atoms being the carboxylate oxygens, but the seven-coordination is not retained in aqueous solution.

Synthesis, characterization and crystal structure of novel mononuclear peroxotungsten(VI) complexes. Insulinomimetic activity of W(VI) and Nb(V) peroxo complexes

Two new mononuclear peroxo complexes of tungsten of the formula (gu)(2)[WO(2)(O(2))(2)] (1) and (gu)[WO(O(2))(2)(quin-2-c)] (2a) (where gu(+)=guanidinium ion, CN(3)H(6)(+) and quin-2-c=quinoline-2-carboxylate ion) have been synthesized and characterized by elemental analysis, infrared, Raman, UV-visible and (1)H NMR spectroscopies. The crystal structure of (gu)[WO(O(2))(2)(quin-2-c)].H(2)O (2b) determined by X-ray diffraction indicates that the side-on peroxo groups and the bidentate quinaldate ligand bind the W(VI) centre leading to an hepta coordination mode. The guanidinium ion occurring as a counterion and the hydrogen-bound interactions stabilize the complexes. The in vitro insulin-mimetic effect of the complexes has been evaluated by the inhibitory effect on free fatty acid release in isolated fat adipocytes treated with epinephrine. Moreover the niobate analogues, synthesized and characterized previously, (gu)(3)[Nb(O(2))(4)] and (gu)(2)[Nb(O(2))(3)(quin-2-c)].H(2)O have been tested for the insulin-like activity.

Enhanced Concentration-Dependent Cytotoxic Effect of the Dinuclear Copper(II) Complex of L-Carnitine [Cu2(L-carnitine)2Cl2(H2O)2]Cl2, Compared to L-Carnitine or Copper Chloride Dihydrate, in Human Leukemic Cell Lines

We studied the antitumor properties of the dinuclear copper(II) complex of l-carnitine [Cu 2( l-carnitine) 2Cl 2(H 2O) 2]Cl 2, as well as those of l-carnitine and copper chloride dihydrate, in human leukemic cells. The complex was synthesized and characterized using EPR, (1)H NMR, (13)C NMR, IR, and UV-vis analyses. Its cytotoxic effect on the human leukemia cell lines HL-60 and K562 was studied by assessing the metabolic activity of cells (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT method), the structural integrity of cell membrane using Trypan blue assay, and the proliferation capacity of cells studying growth curves. Both leukemia cell lines showed a concentration-specific increased cytotoxicity of the complex, compared to l-carnitine or copper chloride dihydrate, with distinct underlying mechanisms, which were decreased proliferation efficiency for HL-60 cells and increased necrotic phenomena for K562 cells. Our results are indicative of a concentration-specific enhanced antileukemic effect of the complex, implying its value as a tool in the implementation of leukemia.

Molybdenum catecholates as models for Mo in biological systems. 1. Synthesis and spectroscopic study on Mo complexes with 3,4-dihydroxybenzoic and 3,4-dihydroxyphenylacetic acid

Abstract Mo(VI) complexes of the ligands 3,4-dihydroxybenzoic acid (3,4-DHBA), protocatechuate (PCA) and 3,4-dihydroxyphenylacetic acid (3,4-DHPA) or DOPAC were formed in aqueous solutions using (NH 4 ) 2 MoO 4 as starting material. Oligomeric complexes were isolated from the solutions as solids, and they were studied via Infrared (IR) and Raman spectroscopies as well as thermogravimetric analysis, in the solid state and in solution via Electrospray Mass Spectra (ESMS) and UV–Vis, Electron Spin Resonance (ESR) and Nuclear Magnetic Resonance (NMR) spectroscopies methods. The ligands were coordinated as catechol and/or semiquinone with the metal. All complexes were found to contain the cis -(MoO 2 ) group, being stable in the presence of air in the solid state. The proposed complex structures are in agreement with all experimental data.

Electrochemical and spectroscopic studies of 2,3-dihydroxybenzoic acid, its oxidation products and their interaction with manganese(II), in dimethyl sulfoxide solutions

The electrochemical and spectroscopic behaviour of 2,3-dihydroxybenzoic acid (2,3-DHBA) and its oxidized forms have been studied in dimethyl sulfoxide solutions under aerobic and anaerobic conditions. The products resulting from the reaction with manganese(II) (in dimethyl sulfoxide) are also studied by cyclic voltammetry, u.v–vis., n.m.r. and e.s.r. spectroscopies. Under anaerobic conditions the anions of the ligand form stable complexes with manganese(II) and (III) of MnL2 type, while in the presence of air the oxidized forms of the ligand react with manganese(II) to give mixed-valence species. The chemical stability of the semiquinone and its manganese complexes in addition to its photosensitivity is noteworthy. Calculations show that the electrogenerated manganese(III)–(2,3-DHB–semiquinone) system is stable, but redox-active and can undergo a two-electron exchange (per monomer). The dimeric (or oligomeric) species should be good candidates for water oxidation studies.

Two novel compounds of vanadium and molybdenum with carnitine exhibiting potential pharmacological use

The reaction of sodium orthovanadate with carnitine hydrochloride molecule results in the precipitation of decavanadate compound of carnitine whereas the reaction of metallic molybdenum with hydrogen peroxide and carnitine results in the peroxo-molybdenum complex of carnitine. The decavanadate compound as well as the molybdenum complex of carnitine have been characterized by means of elemental analysis, IR, electronic spectra, (1)H NMR, 2D-COSY-NMR (=correlation spectroscopy) and thermo-gravimetric analysis (TGA). In addition decavanadate compound of carnitine was fully characterized by X-ray crystallography. The analytical data were in good agreement with the empirical formulae of both, decavanadate compound and molybdenum complex. The two compounds were also evaluated for cell toxicity and their anticancer activity by the MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based assay method, using primary cells and tumor cell lines of both human and murine origins and the results show that compound 1 shows an increased biological activity in comparison with compound 2. Moreover using confocal microscopy and antibodies against cleaved caspase 3 we further analyzed the cell toxicity and we conclude that the apoptotic pathway is triggered efficiently with tumor specificity by compound 1 and not by compound 2.