The periodic table of urea derivative: small molecules of zinc(II) and nickel(II) of diverse antimicrobial and antiproliferative applications.

Two complexes of Zn(II) and Ni(II) ions with the urea derivative, 2-benzimidazolyl-urea (BZIMU), of formulae [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) were synthesized and characterized by their melting point, elemental analysis, spectroscopic techniques (FTIR, UV-Vis and 1H-NMR), High-resolution mass spectroscopy (HRMS), molar conductivity and thermogravimetric analysis. The crystal structures of 1-2 were determined by X-ray diffraction analysis. The antiproliferative activity of 1-2 was tested in vitro against human adenocarcinoma cell lines: cervix (HeLa) and breast (MCF-7). Their toxicity was surveyed against normal human fetal lung fibroblast cells (MRC-5). The bioactivity mechanism of 1-2 and their related analogues of copper and silver metallodrugs are rationalized by the means of computations. The antimicrobial activity of 1-2 against Escherichia coli (E. coli) is also evaluated. The complexes [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) (BZIMU= 2-Benzimidazolyl-urea), were tested in vitro against HeLa and MCF-7 cells. Their toxicity was surveyed against normal MRC-5 cells. The association of the microbiota with the antiproliferative activity of 1-2 was investigated against Escherichia coli.

An Efficient Disinfectant, Composite Material {SLS@[Zn3(CitH)2]} as Ingredient for Development of Sterilized and Non Infectious Contact Lens.

The [Zn3(CitH)2] (1) (CitH4= citric acid), was dispersed in sodium lauryl sulphate (SLS) to form the micelle of SLS@[Zn3(CitH)2] (2). This material 2 was incorporated in hydrogel made by hydroxyethyl-methacrylate (HEMA), an ingredient of contact lenses, toward the formation of pHEMA@(SLS@[Zn3(CitH)2]) (3). Samples of 1 and 2 were characterized by UV-Vis, 1H-NMR, FT-IR, FT-Raman, single crystal X-ray crystallography, X-ray fluorescence analysis, atomic absorption and TG/DTA/DSC. The antibacterial activity of 1-3 as well as of SLS against Gram-positive (Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus)) and Gram-negative (Pseudomonas aeruginosa (PAO1), and Escherichia coli (E. coli)) bacteria was evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and inhibitory zone (IZ). 2 showed 10 to 20-fold higher activity than 1 against the bacteria tested. Moreover the 3 decreases the abundance of Gram-positive microbes up to 30% (St. aureus) and up to 20% (PAO1) the Gram-negative ones. The noteworthy antimicrobial activity of the obtained composite 3 suggests an effective antimicrobial additive for infection-free contact lenses.

A water-soluble silver(I) formulation as an effective disinfectant of contact lenses cases.

The antibacterial effect of the already known water-soluble compound {[Ag6(µ3-Hmna)4(µ3-mna)2]2-·[(Et3NH)+]2·(DMSO)2·(H2O)} (AGMNA) (H2mna = 2­mercapto­nicotinic acid) was evaluated by the mean of the Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC) and the Inhibitory Zone (IZ), against the bacterial strains Pseudomonas aeruginosa (PAO1) and Staphylococcus aureus (St. aureus) which settle in the cornea, in bacterial keratitis. The MICs' of AGMNA against PAO1 and St. aureus were 25.7 ±â€¯2.4 µM and 42.0 ±â€¯0.3 µM respectively. Τhe Biofilm Elimination Concentration (ΒΕC) was used to evaluate the influence of AGMNA on the formation of biofilm of PAO1. AGMNA exhibits stronger antimicrobial activity than that of H2mna or AgNO3. The toxicity of AGMNA was examined against normal human corneal epithelial cells (HCET cells) and by micronucleus (MN) assay in HCET cells. Thus, the IC50 value of AGMNA, towards HCET cells is higher than 120 µΜ, while its effect on MN frequency, of HCET cells, is meaningless, when they are treated with it at 120 µΜ, suggesting no in vitro genotoxicity. The Mitotic Index (MI), Chromosomal Aberrations (CA) and Nuclear Abnormalities (NA) analyses of Allium cepa reveal insignificant variations between treated and untreated ones indicating no in vivo genotoxicity.

Silver ciprofloxacin (CIPAG): a successful combination of chemically modified antibiotic in inorganic-organic hybrid.

The new silver(I) ionic, water soluble, compound {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) was obtained by reacting silver(I) nitrate with the antibiotic ciprofloxacin (CIPH). The complex was characterized by m.p., mid-FT-IR, 1H-NMR, UV-Vis spectroscopic techniques. The crystal structures of both CIPAG and the hexahydrated neutral free drug {[CIPH]∙6(H2O)} (2) were characterized by X-ray crystallography. Two neutral ligands are datively bonded to the metal ion through the piperidinic nitrogen atoms forming a cationic {[Ag(CIPH)2]+} counter part which is neutralized by a nitrate group. The antibacterial effect of CIPAG and the commercially available hydrochloric salt of the antibiotic ({[CIPH 2+ ]∙Cl - } (3)) were tested against the bacterial species Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus) by the mean of minimum inhibitory concentration, minimum bactericidal concentration and their inhibitory zone (IZ). The influence of CIPAG and 3 against the formation of biofilm of PAO1 or St. aureus was also evaluated by mean of biofilm elimination concentration. The IZ caused by CIPAG which has been loaded in poly-hydroxyethylmethacrylate, is determined. The genotoxicity of CIPAG and 3 is tested in vitro against normal human corneal epithelial cells (HCET cells), by the presence of micronucleus in HCET cells and in vivo by mean of Allium cepa test.

New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions.

The new silver(I) compound {[AgBr(µ2-S-MMI)(TPP))]2} (1) and the known one [AgCl(TPP)2(MMI)] (2) were obtained by refluxing toluene solutions of silver(I) halide with triphenylphosphine (TPP) and the anti-thyroid drug 2-mercapto-1-methyl-imidazole or methimazole (MMI). The complexes were characterized by m.p., vibrational spectroscopy (mid-FT-IR), (1)H, (31)P-NMR, UV-Vis spectroscopic techniques and X-ray crystallography. The antibacterial effect of 1 and 2 against the bacterial species Pseudomonas aeruginosa (PAO) and Escherichia coli was evaluated. Compound 1 exhibits comparable activity to the corresponding one of the silver nitrate which is an antibacterial drug in use. The in vivo genotoxicity of 1-2 by the mean of Allium cepa test shows no alterations in the mitotic index values due to the absence of chromosomal aberrations. The mechanism of action of the title compounds is evaluated. The DNA binding tests indicate the ability of the complexes 1-2 to modify the activity of the bacteria. The binding constants of 1-2 towards CT-DNA indicate interaction through opening of the hydrogen bonds of DNA. Docking studies on DNA-complexes interactions confirm the binding of both complexes 1-2 in the major groove of the CT-DNA. In conclusion the silver complex 1 is an anti-bacterial and non-genotoxic material, which can be applied to antibacterial drug in the future.

Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine.

Mixed-ligand silver(I) complexes of formulae [AgCl(TPP)2(MTZD)] (1), {[AgCl(TPP)2(MBZT)]·(MBZT)·2(toluene)} (2), and [AgCl(TPP)2(CMBZT)] (3) were obtained by refluxing toluene solutions of silver(I) chloride with triphenylphosphine (TPP) and the appropriate heterocyclic thioamides 2-mercaptothiazolidine (MTZD), 2-mercaptobenzothiazole (MBZT), and 5-chloro-2-mercaptobenzothiazole (CMBZT). The complexes were characterized by the melting point, vibrational spectroscopy (Fourier transform mid-IR), (1)H-NMR spectroscopy, UV-vis spectroscopy, and X-ray crystallography. DNA binding tests indicate the ability of complexes 1-3 to modify the activity of cells. The binding constants of 1-3 towards calf-thymus DNA (CT-DNA) [(3.5 ± 8.5) × 10(4) M(-1) for 1, (10.0 ± 0.0) × 10(4) M(-1) for 2, and (46.4 ± 7.0) × 10(4) M(-1) for 3] indicate strong interaction of 3. Changes in the fluorescence of ethidium bromide in the presence of DNA suggest intercalation into or electrostatic interactions with DNA. The corresponding apparent binding constants (K app) towards CT-DNA calculated through fluorescence spectra are (3.5 ± 0.7) × 10(4) M(-1) for 1, (10.0 ± 0.0) × 10(4) M(-1) for 2, and (46.4 ± 7.0) × 10(4) M(-1) for 3. Docking studies on DNA complexes confirm the binding of 1 and 2 in the major groove of CT-DNA and of 3 in the minor groove. Moreover, the influence of 1-3 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase was studied kinetically and theoretically. The antibacterial effect of 1-3 against the bacterial species Pseudomonas aeruginosa and Escherichia coli was evaluated. Complex 1 exhibits the strongest activity.

The hsc70 gene which is slightly induced by heat is the main virus inducible member of the hsp70 gene family.

We have found that SV40 infection of CV1 cells induces the synthesis of a 72 kDa protein that upon molecular cloning was shown to be the product of the hsc70 gene. The above gene product was found to be mainly virus inducible, in contrast to the hsp70 gene product which was mainly heat inducible. The two genes were found to be cell cycle regulated in a distinctively different manner.