Various kinds of schiff base metal complexes have been proven to induce apoptosis of tumor cells. However, it remains largely unknown whether schiff base zinc complexes induce apoptosis in human cancer cells. Here, we synthesized a novel schiff base zinc coordination compound (SBZCC) and investigated its effects on the growth, proliferation and apoptosis of human osteosarcoma MG-63 cells. A novel SBZCC was synthesized by chemical processes and used to treat MG-63 cells. The cell viability was determined by CCK-8 assay. The cell cycle progression, mitochondrial membrane potential and apoptotic cells were analyzed by flow cytometry. The apoptosis-related proteins levels were determined by immunoblotting. Treatment of MG-63 cells with SBZCC resulted in inhibition of cell proliferation and cell cycle arrest at G1 phase. Moreover, SBZCC significantly reduced the mitochondrial membrane potential and induced apoptosis, accompanied with increased Bax/Bcl-2 and FlasL/Fas expression as well as caspase-3/8/9 cleavage. Our results demonstrated that the synthesized novel SBZCC could inhibit the proliferation and induce apoptosis of MG-63 cells via activating both the mitochondrial and cell death receptor apoptosis pathways, suggesting that SBZCC is a promising agent for the development as anticancer drugs.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; genetics ; metabolism ; Caspase 8 ; genetics ; metabolism ; Caspase 9 ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coordination Complexes ; chemical synthesis ; pharmacology ; Fas Ligand Protein ; genetics ; metabolism ; G1 Phase Cell Cycle Checkpoints ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; metabolism ; pathology ; Osteoblasts ; drug effects ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Schiff Bases ; chemistry ; Signal Transduction ; Zinc ; chemistry ; bcl-2-Associated X Protein ; genetics ; metabolism ; fas Receptor ; genetics ; metabolism

Whole body integrated magnetic resonance imaging (MR)/positron emission tomography (PET) imaging systems have recently become available for clinical use and are currently being used to explore whether the combined anatomic and functional capabilities of MR imaging and the metabolic information of PET provide new insight into disease phenotypes and biology, and provide a better assessment of oncologic diseases at a lower radiation dose than a CT. This review provides an overview of the technical background of combined MR/PET systems, a discussion of the potential advantages and technical challenges of hybrid MR/PET instrumentation, as well as collection of possible solutions. Various early clinical applications of integrated MR/PET are also addressed. Finally, the workflow issues of integrated MR/PET, including maximizing diagnostic information while minimizing acquisition time are discussed.
Coordination Complexes/chemistry/diagnostic use ; Heart/radiography ; Humans ; *Magnetic Resonance Imaging ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms/pathology/radiography ; *Positron-Emission Tomography ; Radiopharmaceuticals/diagnostic use ; Tomography, X-Ray Computed ; Whole Body Imaging/*standards/*trends

In this paper, the new carbon nanotube modified glassy carbon electrode (F-CNTs/GCE) was prepared to establish a new method for studying the molecular interaction mechanism between baicalin metal complexes (BMC) and bovine serum album (BSA), and the principle of this method was discussed deeply. Under the physiological condition, the thermodynamics and kinetics properties of interaction between BMC and BSA were studied by cyclic voltammetry (CV) to inference their molecular effective mechanism. The results show that the presence of F-CNTs can accelerate the electron transfer, and better response signal was showed in the BMC/BMC-BSA system. The detection of interaction of BMC-BSA used new method show that BMC-BSA generates stable thermodynamically non-covalent compounds, and the obtained average binding sites of BMC-BSA were 1.7; the number of electron transfer in BMC/BMC-BSA reaction process was 2, and non electroactive supramolecular compounds of BMC-BSA were generated by this interacting reaction. The relevant research work provides a new way to study the molecular mechanism for the interaction of drugs with protein, and with a certain reference value for discussion on the non covalent interactions.
Animals ; Cattle ; Coordination Complexes ; chemistry ; Electrodes ; Flavonoids ; chemistry ; Kinetics ; Nanotubes, Carbon ; Serum Albumin, Bovine ; chemistry ; Thermodynamics

OBJECTIVETo establish a method for detecting plasma concentration of corn polysaccharide iron complex (CPIC) and investigate its absorption, distribution and elimination in rats.

METHODSUsing radioactivity isotope tracing method, we detected the radioactivity of (59)Fe-CPIC in the plasma of rats at different time points by gavages of 3 doses (28.0, 14.0, and 7.0 mg/kg) (59)Fe-CPIC in SD rats. The pharmacokinetic parameters was obtained using DAS 2.0 program for analysis of tissue distribution and elimination of (59)Fe-CPIC.

RESULTSThe standard curve was linear within the range of 0.14-141 µg/ml (r=0.9999, n=5). The average recovery was 95% with a relative standard deviation no more than 15%. The pharmacokinetic parameters at 3 doses obtained, namely t1/2 and AUC (0-), were 214∓104, 231∓110, and 181∓81 min, and 1986.3∓513.3, 737.0∓467.0, and 315.1∓226.1 mg·min-1·L(-)1, respectively. (59)Fe-CPIC were detected in all the 13 tissues types examined and high radioactivity intensity was found in the gastrointestinal tract, hematogenic organs and other organs rich in blood. (59)Fe-CPIC was eliminated after intragastric administration primarily via the feces in rats.

CONCLUSIONThe method we established is easy and specific, and the pharmacokinetic parameters of (59)Fe-CPIC fit the two- compartment open model.

Administration, Oral ; Animals ; Area Under Curve ; Coordination Complexes ; administration & dosage ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Intestinal Absorption ; Iron ; administration & dosage ; pharmacokinetics ; urine ; Iron Radioisotopes ; Male ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacokinetics ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; Zea mays ; chemistry

The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi drug resistance. The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from isatin with 3-chloro-4-floroaniline and 2-pyridinecarboxaldehyde with 4-aminoantipyrine have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. FAB mass data show degradation of complexes. Both the ligands behave as bidentate and tridentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. The Schiff base and metal complexes show a good activity against the bacteria; Staphylococcus aureus, Escherichia coli and Streptococcus fecalis and fungi Aspergillus niger, Trichoderma polysporum, Candida albicans and Aspergillus flavus. The antimicrobial results also indicate that the metal complexes are better antimicrobial agents as compared to the Schiff bases. The minimum inhibitory concentrations of the metal complexes were found in the range 10~40 microg/mL.
Ampyrone ; Anti-Infective Agents ; Aspergillus flavus ; Aspergillus niger ; Candida albicans ; Coordination Complexes ; Drug Resistance ; Electronics ; Electrons ; Escherichia coli ; Fungi ; Humans ; Ions ; Isatin ; Ligands ; Magnetics ; Magnets ; Microbial Sensitivity Tests ; Microwaves ; Molar ; Pyridines ; Schiff Bases ; Staphylococcus aureus ; Streptococcus ; Tissue Donors ; Trichoderma

The flavonoid-metal complexes showed obviously stronger bioactivities such as antibiosis, antivirus, anti-inflammatory, anti-tumor and anti-free-radical, possibly because of the stronger binding force caused by the change in complex structure and accessibility to target spots, or the synergy effect between flavonoids and metallic ions. This essay summarizes studies on bioactivity and mechanism of flavonoid-metal complexes, in order to provide reference for in-depth study and development on effective constituents contained in flavonoid traditional Chinese medicines.
Animals ; Coordination Complexes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Humans ; Medicine, Chinese Traditional

This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl2 and FeCl3. The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microgram Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.
Animals ; Brain Ischemia/chemically induced/pathology/therapy ; Cell Differentiation ; Chitosan/*chemistry ; Coordination Complexes/*chemistry/toxicity ; Ferric Compounds/*chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*chemistry/cytology ; Metal Nanoparticles/*chemistry ; Phenotype ; Rabbits

BACKGROUND AND OBJECTIVEThe basic structure of salicylaldehyde-amino acid Schiff base compounds includes a C=N chemical bond. These compounds show significant antitumor activities in vitro when combined with a metal ion. This study investigated the effects and possible mechanisms of four salicylaldehyde-amino acid Schiff base copper ternary coordination compounds on the proliferation of human gastric cancer cell line BGC823.

METHODSThe BGC823 cells were treated with the four compounds (6B, 7B, 6P, and 7P). Cell proliferation was detected by MTT assay. Apoptosis and changes in the cell cycle were analyzed by flow cytometry. DNA damage was observed using a DNA ladder assay. The expression of p53 protein was determined by immunocytochemistry.

RESULTSThe proliferation of BGC823 cells was significantly inhibited by the four compounds and the effect was concentration-dependent. The half maximal inhibitory concentration (IC50) of 6B, 7B, 6P, and 7P for BGC823 cells were 18.10, 27.50, 3.61, and 3.45 micromol/L, respectively. Flow cytometry showed the four drugs induced apoptosis in BGC823 cells, which was confirmed by DNA ladder experiments. Flow cytometry also detected changed phases in the cell cycle from treatment with the compounds. The percent of cells in the G(0)/G(1) phase decreased and that of cells in the G1/S and G(2)/M phases increased, indicating that S-and G2-phase blockages exist. As shown by immunocytochemistry, the expression of p53 decreased in BGC823 cells treated with the four drugs, indicating the involvement of the p53 pathway to BGC823 cell apoptosis.

CONCLUSIONSThe four compounds showed significant activities on restraining proliferation of BGC823 cells in vitro, induced apoptosis, and caused changes in the cell cycle. This may be related to the downregulation of p53.

Aldehydes ; chemistry ; Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coordination Complexes ; chemical synthesis ; pharmacology ; Copper ; chemistry ; Humans ; Inhibitory Concentration 50 ; Schiff Bases ; chemistry ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

Cyclic voltammetric measurements were performed for Co(II), Ni(II), Cu(II) and Zn(II) complexes of 1 : 1 alternating copolymer, poly(3-nitrobenzylidene-1-naphthylamine-co-succinic anhydride) (L) and Ni(II) and Cu(II) complexes of 1 : 1 alternating copolymer, poly(3-nitrobenzylidene-1-naphthylamine-co-methacrylic acid) (L1). The in vitro biological screening effects of the investigated compounds were tested against the fungal species including Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans and bacterial species including Staphylococcus aureus, Escherichia coli, Klebsiella pneumaniae, Proteus vulgaris and Pseudomonas aeruginosa by well diffusion method. A comparative study of inhibition values of the copolymers and their complexes indicates that the complexes exhibit higher antimicrobial activity. Copper ions are proven to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium. The nuclease activity of the above metal complexes were assessed by gel electrophoresis assay and the results show that the copper complexes can cleave pUC18 DNA effectively in presence of hydrogen peroxide compared to other metal complexes. The degradation experiments using Rhodamine B dye indicate that the hydroxyl radical species are involved in the DNA cleavage reactions.
Aspergillus flavus ; Aspergillus niger ; Candida albicans ; Cell Count ; Coordination Complexes ; Copper ; Diffusion ; DNA ; DNA Cleavage ; Electrophoresis ; Escherichia coli ; Hydrogen Peroxide ; Hydroxyl Radical ; Ions ; Klebsiella ; Mass Screening ; Proteus vulgaris ; Pseudomonas aeruginosa ; Rhizoctonia ; Rhizopus ; Rhodamines ; Staphylococcus aureus

PURPOSE: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using [18F] labeled estrogen ligands, especially [18F]FES. However, [18F] has relatively short-lived half-life (t1/2=1.8 h) and the labeling yield of radio-fluorination is usually low compared with 64Cu (t1/2=12.7 h). 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. MATERIALS AND METHODS: 1,7-Protected cyclen, 1,7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). RESULTS: The prepared ligand 1 was fully characterized by 1H, 13C NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes [Cu(1)]2+2(ClO4-) and [Cu(1)Cl]+Cl- which were confirmed by high-resolution mass (FAB). CONCLUSION: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(II) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.
Breast Neoplasms ; Coordination Complexes ; Copper* ; Estradiol ; Estrogens* ; Gadolinium ; Gallium ; Half-Life ; Hydrogen ; Hydrogenation ; Indium ; Ligands ; Phenol ; Positron-Emission Tomography