Spectroscopic and Small-angle X-ray scattering analysis of binding between Copper(II) -1-allylimidazole complex, a potential anti-tumor agent, and bovine serum albumin.

Interactions between transport proteins and compounds with therapeutic potential are pharmacologically important. In this study, using fluorescence, circular dichroism (CD), and small-angle X-ray Scattering (SAXS), we investigated the interaction between bovine serum albumin (BSA) and a copper(II)-1-allylimidazole complex with potential anti-cancer properties. The results revealed dynamic fluorescence quenching of the model carrier protein BSA by the copper(II) complex. The enthalpy change (ΔH), free energy (ΔG), and entropy change (ΔS) were calculated to be 108 kJ/mol, -16.47 kJ/mol, and 419 J/mol K, respectively, according to the Van't Hoff equation. The reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in binding. The results indicate a much lower affinity (Kb âˆ¼ 102-103) for the metal complex compared with similar compounds (Kb âˆ¼ 103-105). CD showed that the studied copper(II) complex does not change the secondary structure of the protein, while SAXS showed that the this compound may attach to the protein surface and stimulate interactions between proteins. The results suggest that the copper(II) complex with 1-allylimidazole binds weakly to BSA, leading to aggregation of albumin in solution, thereby altering its pharmacokinetic properties. The findings are pertinent to drug design.

Experimental and Theoretical Analysis of Metal Complex Diffusion through Cell Monolayer.

The study of drugs diffusion through different biological membranes constitutes an essential step in the development of new pharmaceuticals. In this study, the method based on the monolayer cell culture of CHO-K1 cells has been developed in order to emulate the epithelial cells barrier in permeability studies by laser interferometry. Laser interferometry was employed for the experimental analysis of nickel(II) and cobalt(II) complexes with 1-allylimidazole or their chlorides' diffusion through eukaryotic cell monolayers. The amount (mol) of nickel(II) and cobalt(II) chlorides transported through the monolayer was greater than that of metals complexed with 1-allylimidazole by 4.34-fold and 1.45-fold, respectively, after 60 min. Thus, laser interferometry can be used for the quantitative analysis of the transport of compounds through eukaryotic cell monolayers, and the resulting parameters can be used to formulate a mathematical description of this process.

Selective cytotoxicity and antifungal properties of copper(II) and cobalt(II) complexes with imidazole-4-acetate anion or 1-allylimidazole.

The physicochemical properties of metal complexes determine their potential applications as antitumor agents. In this study, the antitumor properties of mononuclear cobalt(II) and copper(II) coordination compounds (stoichiometry: [Co(iaa)2(H2O)2]·H2O (iaa = imidazole-4-acetate anion), [Co(1-allim)6](NO3)2 (1-allim = 1-allylimidazole), [Cu(iaa)2H2O] and [Cu(1-allim)4(NO3)2]) and their ligands have been evaluated on human lung carcinoma A549 cells and normal bronchial BEAS-2B cells. Designing the chemical structure of new antitumor agents the possible interactions with macromolecules such as DNA or proteins should be take into account. PCR gene tlr4 product served as DNA model, whereas lysozyme and phage-derived endolysin (both peptidoglycan degrading enzymes) were applied as protein/enzyme model. The interactions were analysed using PCR-HRM and circular dichroism, FT-IR, spectrophotometry, respectively. Additionally, the antimicrobial properties of the complexes at a non-cytotoxic concentration were analyzed against S. aureus, E. coli, P. aeruginosa and C. albicans strains. The results obtained in this study showed the selective cytotoxicity of metal complexes, mainly [Cu(1-allim)4(NO3)2] towards tumor cells. From all tested compounds, only [Co(iaa)2(H2O)2].H2O non-covalently interacts with DNA. Cu(II) and Co(II) complexes did not affect the secondary conformation of tested proteins but modified the hydrolytic activity of enzymes (lysozyme and endolysin). Moreover, only [Co(iaa)2(H2O)2].H2O exhibited the antifungal properties. In conclusion, Co(II) and Cu(II) metal complexes bearing two imidazole-4-acetate ligands seemed to be promising antitumor and antifungal agents for future drug design and application.

The effects of nickel(II) complexes with imidazole derivatives on pyocyanin and pyoverdine production by Pseudomonas aeruginosa strains isolated from cystic fibrosis.

Pseudomonas aeruginosa infection is problematic in patients with cystic fibrosis (CF). P. aeruginosa secretes a diversity of pigments, such as pyocyanin and pyoverdine. The aim of this study was to evaluate the effects of complexes of nickel(II) ([Ni(iaa)2(H2O)2]·H2O (iaa = imidazole-4-acetate anion), [Ni(1-allim)6](NO3)2 (1-allim = 1-allylimidazole) and NiCl2 on pyocyanin and pyoverdine production by 23 strains of P. aeruginosa isolated from cystic fibrosis under growth conditions specific for the CF respiratory system. The antibacterial effects and biophysical properties of the tested substances were measured by spectrofluorometric techniques, as well as by laser interferometry, confocal and atomic force microscopy. The cytotoxic properties of all compounds were measured by Annexin/IP assay against A549 cells. All tested compounds have no effect on pyocyanin production and decrease the pyoverdine secretion in about 40% of tested P. aeruginosa strains at non-cytotoxic range of concentrations. Imidazole-4-acetate anion and 1-allylimidazole have good diffusion properties in the mature P. aeruginosa PAO1 biofilm. In conclusion, the tested nickel(II) complexes do not have clinical implications in P. aeruginosa eradication in cystic fibrosis. The diffusion properties of 1-allylimidazole and imidazole-4-acetate and their lack of effect on A549 cells suggest that they might be considered for chemical synthesis with other transition metals.