Synthesis, characterization, and antibacterial and anticancer screening of {M(2+)-Co (3+)-M (2+)} and {Co (3+)-M (2+)} (M is Zn, Cd, Hg) heterometallic complexes.

The cobalt(III) complexes Et(4)N[Co(L(1))(2)] and [Co(L(2))(3)] [H(2)L(1) is 2,6-bis(N-(2-pyridyl)carbamoyl)pyridine and HL(2) is 2-(N-(2-pyridyl)carbamoyl)pyridine] were used as the building blocks for preparing a series of {M(2+)-Co(3+)-M(2+)} (where M is Zn, Cd, or Hg) and {Co(3+)-M(2+)} (where M is Zn or Cd) heterometallic complexes. All heterometallic complexes were characterized using a host of spectroscopic methods (IR, NMR, and UV/vis spectroscopy and mass spectrometry), elemental analysis, and conductivity measurements. One of the representative compounds, {Hg(2+)-Co(3+)-Hg(2+)}, was characterized crystallographically, and it was revealed that two Hg(II) ions are coordinated within the clefts created by the building block Et(4)N[Co(L(1))(2)]. The results of screening for anticancer activity against the human brain tumor U87 cell line and antibacterial activity against a range of resistant (Pseudomonas aeruginosa and Proteus vulgaris) as well as standard (Staphylococcus aureus SA 96, P. aeruginosa MTCC 1688, Klebsiella planticola MTCC 2272, and Escherichia coli T7) bacterial strains indicate promising activities. Notably, the observed activity was found to vary with the type of building block and the secondary metal ion present in the heterometallic complex. Treatment-induced cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT and macrocolony assay), growth inhibition, cytogenetic damage, cell cycle delay, and apoptosis were studied as the parameters for cellular response.

Fabrication and growth mechanism of ZnO nanostructures and their cytotoxic effect on human brain tumor U87, cervical cancer HeLa, and normal HEK cells.

ZnO nanostructures of diverse shape were grown via a solution process with different precursors and conditions. Morphological investigation of the nanostructures was carried out using field emission scanning electron microscopy and transmission microscopy observations and revealed that the nanostructures exhibit a wurtzite phase with an ideal lattice fringe distance of approximately 0.52 nm. The powder crystallinity was examined via X-ray diffraction spectroscopy. Screening results from anticancer studies of the effects on human brain tumor U87, cervical cancer HeLa, and normal HEK cells of ZnO nanostructures of diverse shape were obtained and indicate promising activity that varies with changes in the structure and the size of the particles. Treatment-induced cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and survival assay], growth inhibition, cytogenetic damage (formation of micronuclei), and apoptosis were studied as parameters for the cellular response. Treatment with nanostructures enhanced growth inhibition and cell death in a concentration-dependent manner in both U87 and HeLa cell lines. At higher concentrations (above 15.6 µg/ml) the cytotoxic effects of the nanoparticles were highly synergistic and mainly mediated through apoptosis, implying the possible interactions of lesions caused by the agents. The enhanced cell death due to nanoparticles was accompanied by a significant increase (2-3 fold at 31.25 µg/ml) in the formation of micronuclei in U87 cells. The increase in the formation of micronuclei observed after treatment indicates that these structures may interfere with the rejoining of DNA strand breaks. Among all the nanostructures, nanoparticles and sheets exhibited potent activity against both HeLa and U87 cells. However, despite potent in vitro activity, all nanostructures exhibited diminished cytotoxicity against normal human HEK cells at all effective concentrations.

Synthesis, characterization and antibacterial activity of cobalt(III) complexes with pyridine-amide ligands.

The ligands 2-(N-(X-pyridyl)carbamoyl)pyridine (X=2, 3 or 4 for HL1-HL3, respectively) and 2,6-bis(N-(Y-pyridyl)carbamoyl)pyridine (Y=2, 3 or 4 for H2L4-H2L6, respectively) in their mono- and di-deprotonated forms have been used to synthesize kinetically stable cobalt(III) compounds [Co(L1-3)3] (1-3) and Na[Co(L4-6)2] (4-6), respectively. The Co(III) ion is in octahedral environment and is surrounded by three bidentate ligands in complexes 1-3 and two tridentate ligands in complexes 4-6. Ligands coordinate the cobalt center via amidic-N and pyridine-N centers forming a 5-membered chelate ring. Complexes 1-6 have thoroughly been characterized by the various spectroscopic analyses (1H NMR, 13C NMR, UV-vis, IR, mass), elemental analysis, and conductivity measurement. All complexes have been assayed for in vitro antimicrobial activity against clinically isolated resistant strains of Pseudomonas, Proteus, Escherichia coli and standard strains of Pseudomonas aeruginosa (MTCC 1688), Shigella flexneri (MTCC 1457), Klebsiella planticola (MTCC 2272). All cobalt compounds show mild to moderate activity. However, complexes [Co(L1)3] (1) and Na[Co(L4)2] (4) were found to have potent activity against standard and pathogenic resistant bacteria used in the study. Their MIC ranged from 2.7 to 187 microg/ml. In vitro toxicity tests demonstrated that all complexes were less cytotoxic than that of gentamycin on HEK cell lines and the results reveal that these complexes can act as potent antimicrobial agents.

Altered antioxidant system stimulates dielectric barrier discharge plasma-induced cell death for solid tumor cell treatment.

This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center, Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. Detailed investigation of biological effects occurring after atmospheric pressure non-thermal (APNT) plasma application during in vitro experiments revealed the role of reactive oxygen species (ROS) in modulation of the antioxidant defense system, cellular metabolic activity, and apoptosis induction in cancer cells. To understand basic cellular mechanisms, we investigated the effects of APNT DBD plasma on antioxidant defense against oxidative stress in various malignant cells as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity, and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery, with compromised redox status, might have led to sensitization of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues.

Synthesis, structure and biological activity of copper(II) complexes of 4-(2-pyridylmethyl)-1,7-dimethyl-1,4,7-triazonane-2,6-dione and 4-(2-pyridylethyl)-1,7-dimethyl-1,4,7-triazonane-2,6-dione.

Four mononuclear copper(II) complexes 1-4 have been synthesized with two new N-functionalized macrocyclic ligands L(1) and L(2). All complexes are well characterized by various spectroscopic techniques, elemental analyses and conductivity measurements. Results suggest that Cu(II) ion has N(2)O coordination from ligand and S(2) from two coordinated solvent molecules (SCH(3)CN for 1 and 3 while CH(3)OH for 2 and 4). The crystal structure of a representative complex 3 strengthen the proposed formulations for other isostructural copper(II) complexes. The structure of 3 shows few interesting features including rare bent mode of the coordinated CH(3)CN molecules. All complexes were assayed for in vitro antimicrobial activity against clinically isolated resistant strains of Pseudomonas aeruginosa and Proteus vulgaris; and standard strains of Staphylococcus aureus, P. aeruginosa, Klebsiella planticola and Escherichia coli. Results indicate that the copper complexes possess notable antimicrobial properties with MIC values of 62.5-500 microg/ml. Studies on the U87 cancerous cell lines show potent cytotoxicity with IC(50) and IC(90) values of 2.9-93.5 and 30-250 microg/ml, respectively. In vitro toxicity tests demonstrate that all copper complexes are less cytotoxic than that of gentamycin on normal HEK cell lines. These copper complexes show the potential to act as antimicrobial and anticancer agent.