Search

Fourteen cobalt(II) complexes with the non-steroidal anti-inflammatory drugs sodium meclofenamate, tolfenamic acid, mefenamic acid, naproxen, sodium diclofenac, and diflunisal were prepared in the presence or absence of a series of nitrogen-donors (namely imidazole, pyridine, 3-aminopyridine, neocuproine, 2,2'-bipyridine, 1,10-phenanthroline and 2,2'-bipyridylamine) as co-ligands and were characterised by spectroscopic and physicochemical techniques. Single-crystal X-ray crystallography was employed to determine the crystal structure of eight complexes. The biological profile of the complexes was investigated regarding their interaction with serum albumins and DNA, and their antioxidant potency. The interaction of the compounds with calf-thymus DNA takes place via intercalation. The ability of the complexes to cleave pBR322 plasmid DNA at the concentration of 500 μM is rather low. The complexes demonstrated tight and reversible binding to human and bovine serum albumins and the binding site of bovine serum albumin was also examined. In order to assess the antioxidant activity of the compounds, the in vitro scavenging activity towards free radicals, namely 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and their ability to reduce H 2 O 2 were studied.

Copper(II) complexes with an α-diimine show a wide variety of biological activities, such as antibacterial, antifungal, antioxidant and anticancer. In this work, we synthesized and structurally characterized two novel Cu(II) complexes with methyl 3-formyl-4-hydroxybenzoate (HL) and α-diimines: 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen). Crystal structure analysis shows that the formulas of the compounds are [Cu(bipy)(L)(BF 4 )] (1) and [Cu(phen)(L)(H 2 O)](BF 4 )·H 2 O (2), with BF 4 - as a ligand in complex 1, which is rarely coordinated to metals. Both complexes have a square pyramidal geometry, while DFT calculations showed that the most stable structures of complexes 1 and 2 in a water/DMSO mixture are square-planar derivatives [Cu(bipy)(L)] + and [Cu(phen)(L)] + . The antibacterial activity of compounds was evaluated in vitro on four Gram-negative and four Gram-positive bacterial strains. Complex 2 showed greater antibacterial activity towards all bacterial strains comparable to the control compound Amikacin. Complex 2 exerted a strong cytotoxic effect against the tested cancer cell lines (IC 50 values ranging from 0.32 to 0.44 μM). Both complexes caused apoptotic cell death in HeLa cells and a noticeable in vitro antiangiogenic effect. In the concentration range of 5 to 100 μM, the complexes showed the absence of a genotoxic effect and displayed a protective effect against oxidative DNA damage induced by H 2 O 2 in human peripheral blood cells. The interaction between the compounds and calf-thymus DNA was evaluated by diverse techniques suggesting a tight binding, which was also confirmed by molecular docking. In addition, it was found that the complexes bind tightly and reversibly to bovine and human serum albumin.

Five neutral zinc(II) complexes of 3-bromo-5-chloro-salicylaldehyde (3-Br-5-Cl-saloH) were synthesized in the absence or presence of the nitrogen-donor co-ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) and were characterized by various techniques. The obtained complexes were [Zn(3-Br-5-Cl-salo) 2 (H 2 O) 2 ] (1), [Zn(3-Br-5-Cl-salo) 2 (bipy)] (2), [Zn(3-Br-5-Cl-salo) 2 (phen)] (3), [Zn(3-Br-5-Cl-salo) 2 (neoc)] (4) and [Zn(3-Br-5-Cl-salo) 2 (bipyam)] (5). The crystal structures of complexes 1 and 3 were determined by single-crystal X-ray crystallography. The interaction of the compounds with calf-thymus DNA takes place via intercalation. The compounds may moderately cleave pBR322 plasmid DNA at a concentration of 500 μM. The compounds may bind tightly and reversibly to serum albumins. The antioxidant activity of the compounds was examined towards 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and H 2 O 2 . The antimicrobial potency of the compounds was investigated against Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli NCTC 29212 and Xanthomonas campestris ATCC 1395.

Two novel halogenated (Br- and F-) quinazoline derivatives, namely [( E )-4-(2-((6-bromopyridin-2-yl)methylene)hydrazinyl)quinazoline] (L1) and [( E )-4-(2-((3-fluoropyridin-2-yl)methylene)hydrazinyl) quinazoline] (L2), were synthesized and characterized. Their interaction with a series of metal(II) ions (= Mn(II), Ni(II), Cu(II), Zn(II) and Cd(II)) resulted in the formation of six mononuclear complexes characterized by spectroscopic techniques and single-crystal X-ray crystallography. The complexes bear the formulae [Ni(L 1 ) 2 ](NO 3 ) 2 (1), [Zn(L 2 ) 2 ](NO 3 )(PF 6 ) (2), [Cd(L 2 )(H 2 O)(CH 3 OH)(NO 3 )](NO 3 ) (3), [Cu(L 2 )Cl 2 ] (4), [Ni(L 2 ) 2 ](NO 3 ) 2 (5) and [Mn(L 2 )(CH 3 OH)(Cl) 2 ] (6). The biological activity of the compounds was further evaluated in vitro regarding their interaction with calf-thymus DNA, their cleavage ability towards supercoiled circular pBR322 plasmid DNA in the absence or presence of irradiation at various wavelengths (UVA, UVB and visible light), their affinity to bovine serum albumin and their ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H 2 O 2 . In silico molecular docking calculations were employed to study the behavior of the complexes towards calf-thymus DNA and bovine serum albumin.

Aminated silica hybrid, spin-crossover (SCO) nanoparticles (AmNPs) coupled with ( S )-naproxen (NAP) were proposed for potential drug nanocarriers through drug release experiments at various pH values. DNA- and albumin-binding studies were also carried out using diverse techniques in order to investigate the interaction of the nanoparticles with calf-thymus DNA and serum albumins and to determine the corresponding binding constants.

In recent years, there has been an increasing interest in the study of Ag(I) coordination compounds as potent antibacterial and anticancer agents. Herein, a series of Ag(I) complexes bearing phosphines and heterocyclic thioamide ligands with highly electronegative NH 2 - and CF 3 -group substituents, i.e. [AgCl(atdztH)(xantphos)] (1), [Ag(μ-atdztH)(DPEphos)] 2 (NO 3 ) 2 (2), [Ag(atdzt)(PPh 3 ) 3 ] (3), [Ag(μ-atdzt)(DPEphos)] 2 (4), and [Ag(μ-mtft)(DPEphos)] 2 (5), where atdztH = 5-amino-1,3,4-thiadiazole-2-thiol, mtftH = 4-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and DPEphos = bis(2-diphenylphosphino-phenyl)ether, were synthesized, and their in vitro antibacterial and anticancer properties were evaluated. Complexes 1-4 bearing the NH 2 -substituted thioamide exhibited moderate-to-high activity against S. aureus , B. subtilis , B. cereus and E. coli bacterial strains. A high antiproliferative activity was also observed for 1-3 against SKOV-3, Hup-T3, DMS114 and PC3 cancer cell lines (IC 50 = 4.0-11.7 μM), as well as some degree of selectivity against MRC-5 normal cells. Interestingly, 5 bearing the CF 3 -substituted thioamide is completely inactive in all bioactivity studies. Binding of 1-3 to drug-carrier proteins BSA and HSA is reasonably strong for their uptake and subsequent release to possible target sites. The three complexes show a significant in vitro antioxidant ability for scavenging free radicals, suggesting likely implication of this property in the mechanism of their bioactivity, but a low potential to destroy the double-strand structure of CT-DNA by intercalation. Complementary insights into possible bioactivity mechanisms were provided by molecular docking calculations, exploring the ability of complexes to bind to bacterial DNA gyrase, and to the overexpressed in the aforementioned cancer cells Fibroblast Growth Factor Receptor 1, affecting their functionalities.

The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

The interaction of Zn(II) with the non-steroidal anti-inflammatory drug tolfenamic acid leads to the formation of the structurally characterized trinuclear [Zn(3)(tolfenamato)(6)(CH(3)OH)(2)] complex. In the presence of the N,N'-donor heterocyclic ligands 1,10-phenanthroline and 2,2'-bipyridine at a range of ratios, the mononuclear Zn complexes of the general formulae [Zn(tolfenamato)(N,N'-donor)Cl] and [Zn(tolfenamato)(2)(N,N'-donor)] have been isolated and structurally characterized by X-ray crystallography. The deprotonated tolfenamato ligands are coordinated to the Zn(II) ion through carboxylato oxygen atoms. Tolfenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Zinc complexes with the third-generation quinolone antibacterial drugs levofloxacin and sparfloxacin have been synthesized and characterized. The deprotonated quinolones act as bidentate ligands coordinated to zinc ion through the pyridone and a carboxylato oxygen atom. The crystal structures of [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10-phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have revealed that they can bind to CT DNA probably by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The DNA binding constants have been also calculated. A competitive study with ethidium bromide (EB) showed that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The interaction of the complexes with human and bovine serum albumin proteins has been studied by fluorescence spectroscopy showing that the complexes exhibit good binding propensity to these proteins having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the previously reported Zn(II) complexes with the first- and second-generation quinolones oxolinic acid and enrofloxacin.

Copper(II) complexes with the non-steroidal antiinflammatory drug mefenamic acid in the presence of aqua or nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized. The crystal structures of [(2,2'-bipyridine)bis(mefenamato)copper(II)], 2, [(2,2'-bipyridylamine)bis(mefenamato)copper(II)], 4, and [bis(pyridine)bis(methanol)bis(mefenamato)copper(II)], 5, have been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [bis(aqua)tetrakis(mefenamato)dicopper(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the complexes can bind to CT DNA by the intercalative binding mode verified also by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Mefenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. All the compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity., (This journal is © The Royal Society of Chemistry 2011)

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid in the presence or absence of nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The experimental data suggest that mefenamic acid acts as deprotonated monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structures of tetrakis(methanol)bis-(mefenamato)cobalt(II), 1 and (2,2'-bipyridine)bis(methanol)bis(mefenamato)cobalt(II), 2 have been determined by X-ray crystallography. The EPR spectra of complexes 1 and 2 in frozen solution reveal that they retain their structures. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and bis(methanol)bis(pyridine)bis-(mefenamato)cobalt(II) exhibits the highest binding constant. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in dmso solution and in the presence of CT DNA in 1 : 2 dmso : buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode. Mefenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.