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  Subjects -> CHEMISTRY (Total: 831 journals)
    - ANALYTICAL CHEMISTRY (47 journals)
    - CHEMISTRY (584 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (26 journals)
    - INORGANIC CHEMISTRY (41 journals)
    - ORGANIC CHEMISTRY (45 journals)
    - PHYSICAL CHEMISTRY (66 journals)

INORGANIC CHEMISTRY (41 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 11)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 2)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 5)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 1)
Current Methods in Inorganic Chemistry     Full-text available via subscription   (Followers: 1)
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 7)
European Polymer Journal     Hybrid Journal   (Followers: 43)
Heterocyclic Communications     Hybrid Journal   (Followers: 1)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 5)
Inorganic Chemistry     Full-text available via subscription   (Followers: 20)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 8)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 1)
Inorganic Materials     Hybrid Journal   (Followers: 3)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 4)
Inorganics     Open Access  
International Journal of Inorganic Chemistry     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 4)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 7)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic Chemistry     Open Access   (Followers: 2)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 9)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 9)
Metallodrugs     Open Access   (Followers: 1)
Open Journal of Inorganic Chemistry     Open Access   (Followers: 3)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 11)
Polyoxometalate Chemistry     Open Access  
Reviews in Inorganic Chemistry     Hybrid Journal  
Russian Journal of Inorganic Chemistry     Hybrid Journal  
Studies in Inorganic Chemistry     Full-text available via subscription  
Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry     Hybrid Journal   (Followers: 2)
Topics in Inorganic and General Chemistry     Full-text available via subscription  
Zeitschrift für anorganische und allgemeine Chemie     Hybrid Journal   (Followers: 1)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover   Journal of Inorganic Biochemistry
  [SJR: 0.96]   [H-I: 87]   [2 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [2800 journals]
  • Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving
           groups ­ a rational approach towards exploiting the platinum(IV)
           prodrug strategy
    • Abstract: Publication date: Available online 28 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Doris Höfer, Hristo Varbanov, Anton Legin, Michael A. Jakupec, Alexander Roller, Markus Galanski, Bernhard K. Keppler
      A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)2(OCOR’)(OCOR”)], where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear (1H, 13C, 15N, 195Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines deriving from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin resistant colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC50 values in the low micromolar and even nanomolar range demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands.
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      PubDate: 2015-08-29T20:28:48Z
       
  • Factors Affecting the Aluminium Content of Human Femoral Head and Neck
    • Abstract: Publication date: Available online 28 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Anetta Zioła-Frankowska, Mikołaj Dąbrowski, Łukasz Kubaszewski, Piotr Rogala, Marcin Frankowski
      Tissues for the study were obtained intraoperatively during hip replacement procedures from 96 patients. In all the cases, the indication for this treatment were primary or secondary degenerative changes in the hip joint. The subject of the study was the head and neck of the femur, resected in situ. Aluminium concentrations measured in femoral head and neck samples from patients aged between 25 and 91 were varied. Statistical methods were applied to determine the variations in relation to the parameters from the background survey. Significant differences in the aluminium content of femoral head samples were observed between patients under and over 60years of age. Based on the results, it was confirmed that the aluminium accumulates in bones over a lifetime. The study showed that the content of aluminium in the head and neck of the femur depends on the factors such as: type of medicines taken, contact with chemicals at work, differences in body anatomy and sex. The study on the levels of aluminium in bones and the factors affecting its concentration is a valuable source of information for further research on the role of aluminium in bone diseases. Based on the investigations, it was found that the GF-AAS technique is the best analytical tool for routine analysis of aluminium in complex matrix samples. The use of femoral heads in the investigations was approved by the Bioethics Committee of the University of Medical Sciences in Poznań (Poland).
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      PubDate: 2015-08-29T20:28:48Z
       
  • Differential Activation of Genes Related to Aluminium Tolerance in Two
           Contrasting Rice Cultivars
    • Abstract: Publication date: Available online 28 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Maite Roselló, Charlotte Poschenrieder, Benet Gunsé, Juan Barceló, Mercè Llugany
      Rice (Oryza sativa) is a highly Al-tolerant crop. Among other mechanisms, a higher expression of STAR1/STAR2 (sensitive to Al rhizotoxicity1/2) genes and of Nrat1 (NRAMP Aluminium Transporter 1), and ALS1 (Aluminium sensitive 1) can at least in part be responsible for the inducible Al tolerance in this species. Here we analysed the responses to Al in two contrasting rice varieties. All analysed toxicity/tolerance markers (root elongation, Evans blue, morin and haematoxylin staining) indicated higher Al-tolerance in variety Nipponbare, than in variety Modan. Nipponbare accumulated much less Al in the roots than Modan. Aluminium supply caused stronger expression of STAR1 in Nipponbare than in Modan. A distinctively higher increase of Al-induced abscisic acid (ABA) accumulation was found in the roots of Nipponbare than in Modan. Highest ABA levels were observed in Nipponbare after 48h exposure to Al. This ABA peak was coincident in time with the highest expression level of STAR1. It is proposed that ABA may be required for cell wall remodulation facilitated by the enhanced UDP-glucose transport to the walls through STAR1/STAR2. Contrastingly, in the roots of Modan the expression of both Nrat1 coding for a plasma membrane Al-transporter and of ALS1 coding for a tonoplast–localized Al transporter was considerably enhanced. Moreover, Modan had a higher Al-induced expression of ASR1 a gene that has been proposed to code for a reactive oxygen scavenging protein. In conclusion, the Al -exclusion strategy of Nipponbare, at least in part mediated by STAR1 and probably regulated by ABA, provided better protection against Al toxicity than the accumulation and internal detoxification strategy of Modan mediated by Nrat1, ALS1 and ARS1.
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      PubDate: 2015-08-29T20:28:48Z
       
  • Aluminum and its effect in the equilibrium between folded/unfolded
           conformation of NADH
    • Abstract: Publication date: Available online 29 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Elena Formoso, Jon I. Mujika, Slawomir J. Grabowski, Xabier Lopez
      Nicotinamide adenine dinucleotide (NADH) is one of the most abundant cofactor employed by proteins and enzymes. The molecule is formed by two nucleotides that can lead to two main conformations: folded/closed and unfolded/open. Experimentally, it has been determined that the closed form is about 2kcal/mol more stable than the open formed. Computationally, a correct description of the NADH unfolding process is challenging due to different reasons: 1) The unfolding process shows a very low energy difference between the two conformations 2) The molecule can form a high number of internal hydrogen bond interactions 3) Subtle effects such as dispersion may be important. In order to tackle all these effects, we have employed a number of different state of the art computational techniques, including: a) well-tempered metadynamics, b) geometry optimizations, and c) Quantum Theory of Atoms in Molecules (QTAIM) calculations, to investigate the conformational change of NADH in solution and interacting with aluminum. All the results indicate that aluminum indeed favors the closed conformation of NADH, due mainly to the formation of a more rigid structure through key hydrogen bond interactions.
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      PubDate: 2015-08-29T20:28:48Z
       
  • Cationic Pd(II)/Pt(II) 5,5-diethylbarbiturate complexes with
           bis(2-pyridylmethyl)amine and terpyridine: Synthesis, structures, DNA/BSA
           interactions, intracellular distribution, cytotoxic activity and induction
           of apoptosis
    • Abstract: Publication date: Available online 29 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Ceyda Icsel, Veysel T. Yilmaz, Yunus Kaya, Selvi Durmus, Mehmet Sarimahmut, Orhan Buyukgungor, Engin Ulukaya

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      PubDate: 2015-08-29T20:28:48Z
       
  • New platinum(II)-bipyridyl corrole complexes: Synthesis, characterization
           and binding studies with DNA and HSA
    • Abstract: Publication date: Available online 29 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Bernardo A. Iglesias, Joana F.B. Barata, Patrícia M.R. Pereira, Henrique Girão, Rosa Fernandes, João P.C. Tomé, Maria G.P.M.S. Neves, José A.S. Cavaleiro
      A simple methodology giving access to the metal-free corroles of trans-A2B type, 5,15-bis(pentafluorophenyl)-10-{3-[2-(pyridin-4-yl)vinyl]phenyl}corrole and 5,15-bis(pentafluorophenyl)-10-{4-[2-(pyridin-4-yl)vinyl]phenyl}corrole, and to the corresponding bipyridyl platinum(II) complexes is described. These new positional isomers were fully characterized and spectroscopic studies demonstrated the ability of Pt(II)-corrole complexes to establish non-covalent interactions with calf-thymus DNA (ct-DNA) and human serum albumin (HSA). Additionally, gel electrophoresis experiments demonstrated that Pt(II)-corrole complexes are able to bind plasmid pMT123 DNA, inducing alterations on its secondary structure.


      PubDate: 2015-08-29T20:28:48Z
       
  • Aluminium leaching from red mud by filamentous fungi
    • Abstract: Publication date: Available online 29 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Martin Urík, Marek Bujdoš, Barbora Milová-Žiaková, Petra Mikušová, Marek Slovák, Peter Matúš
      This contribution investigates the efficient and environmentally friendly aluminium leaching from red mud (bauxite residue) by 17 species of filamentous fungi. Bioleaching experiments were examined in batch cultures with the red mud in static, 7-day cultivation. The most efficient fungal strains in aluminium bioleaching were Penicillium crustosum G-140 and Aspergillus niger G-10. The A. niger G-10 strain was capable to extract up to approximately 141mg.L−1 of aluminium from 0.2g dry weight red mud. Chemical leaching with organic acids mixture, prepared according to A. niger G-10 strain’s respective fungal excretion during cultivation, proved that organic acids significantly contribute to aluminium solubilization from red mud.
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      PubDate: 2015-08-29T20:28:48Z
       
  • Effects of gold complexes on the assembly behavior of human islet amyloid
           polypeptide
    • Abstract: Publication date: Available online 29 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Lei He, Dengsen Zhu, Cong Zhao, Xian Jia, Xuesong Wang, Weihong Du
      Human islet amyloid polypeptide (hIAPP) is a well-known amyloid protein that is associated with type II diabetes. Inhibitors of this peptide include aromatic organic molecules, short peptides, and metal complexes, such as zinc, ruthenium and vanadium compounds. Various metal ions and their complexes affect the fibrillization of hIAPP in different action modes. However, the assembly mechanism of the peptide remains unclear. This study evaluated the inhibitory effects of three gold complexes with different nitrogen-containing aromatic ligands, namely, [Au(bipy)Cl2][PF6] (1), [Au(Ph2bpy)Cl2]Cl (2), and [Au(phen)Cl2]Cl (3), on the amyloid fibrillization of hIAPP. The complexes interacted with the peptide mainly through hydrophobic interaction and metal coordination. The concentration dependence of hIAPP aggregation on gold complex indicated that the assembly behavior of hIAPP is significantly affected by these compounds. The gold complexes inhibited peptide aggregation through dimerization and stabilized the peptide to monomers. Gold ion was found to be a key influencing factor of the binding mode and assembly behavior of hIAPP. The different effects of the complexes on peptide aggregation might be attributed to their special ligands. This study provided insights into the inhibitory mechanism of gold complexes against hIAPP fibrillization.
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      PubDate: 2015-08-29T20:28:48Z
       
  • In vitro antitumor activity of free and nano-encapsulated
           Na5[PMo10V2O40].nH2O and its binding properties with ctDNA by using
           combined spectroscopic methods
    • Abstract: Publication date: Available online 24 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Somayeh Dianat, Abdol-Khalegh Bordbar, Shahram Tangestaninejad, Bahram Yadollahi, Razieh Amiri, Sayyed- Hamid Zarkesh-Esfahani, Parvin Habibi
      Free and nanosized starch and lipid encapsulated Na5[PMo10V2O40].nH2O complexes (abbreviated as PMoV, SEP and LEP, respectively) have been prepared and structurally characterized by Fourier transform infrared (FT-IR) spectroscopy, inductively coupled plasma (ICP) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. The results show that the PMoV retains its parent structure after encapsulation by starch and lipid nanoparticles. The in vitro antitumor activity of PMoV in its free and nano-encapsulated forms was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay that was carried out on two types of human cancer cells, MCF-7 (breast cancer cells) and HEK-293 (Human Embryonic Kidney). The results represent the enhancement of cell penetration and antitumor activity of PMoV due to its encapsulation in starch or lipid nanoparticles. However, this observed enhancement for the lipid relative to the starch nanocapsule can be attributed to its smaller size. In order to investigate the molecular nature of antitumor activity, the binding properties of PMoV with calf thymus DNA (ctDNA) were also comprehensively evaluated using UV–vis absorption spectroscopy, fluorescence quenching and fluorescence Scatchard plots. The results rule out the intercalating binding mode and propose the groove or outside stacking binding for PMoV. However, a biphasic binding behavior that is due to the change in the binding mode was observed by varying of [PMoV]/[ctDNA] mole ratio. The results of cell culture assay and DNA binding experiments represent that the rate of cell penetration is more important than DNA binding affinity in the antitumor activity for POM.
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      PubDate: 2015-08-25T20:25:22Z
       
  • Effects of aluminium chloride and aluminium chlorohydrate on DNA repair in
           MCF10A immortalised non-transformed human breast epithelial cells
    • Abstract: Publication date: Available online 15 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): A. Farasani, P.D. Darbre
      Use of underarm aluminium (Al) -based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Long-term (19–21 weeks) exposure to Al chloride or Al chlorohydrate at a 10−4 M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis.
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      PubDate: 2015-08-18T04:14:04Z
       
  • Identification of Differential Anti-Neoplastic Activity of Copper
           Bis(Thiosemicarbazones) that is Mediated by Intracellular Reactive Oxygen
           Species Generation and Lysosomal Membrane Permeabilization
    • Abstract: Publication date: Available online 17 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Christian Stefani, Zaynab Al-Eisawi, Patric J. Jansson, Danuta S. Kalinowski, Des R. Richardson
      Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) CuII/I redox potentials; (2) ability to induce cellular 64Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-L-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones).
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      PubDate: 2015-08-18T04:14:04Z
       
  • The Adsorption of Allergoids and 3-O-desacyl-4’- monophosphoryl
           lipid A (MPL®) to Microcrystalline Tyrosine (MCT) in Formulations for
           use in Allergy Immunotherapy
    • Abstract: Publication date: Available online 15 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): A.J. Bell, M.D. Heath, S.J. Hewings, M.A. Skinner
      Infectious disease vaccine potency is affected by antigen adjuvant adsorption. WHO and EMA guidelines recommend limits and experimental monitoring of adsorption in vaccines and allergy immunotherapies. Adsorbed allergoids and MPL® in MATA-MPL allergy immunotherapy formulations effectively treats IgE mitigated allergy. Understanding vaccine antigen adjuvant adsorption allows optimisation of potency and should be seen as good practice; however current understanding is seldom applied to allergy immunotherapies. The allergoid and MPL® adsorption to MCT in MATA-MPL allergy immunotherapy formulations was experimental determination using specific allergen IgE allerginicity and MPL® content methods. Binding forces between MPL® and MCT was investigated by competition binding experiments. MATA-MPL samples with different allergoids gave results within 100-104% of the theoretical 50μg/ml MPL® content. Unmodified drug substance samples showed significant desirable IgE antigenicity, 1040 – 170 QAU/ml. MATA-MPL supernatant samples with different allergoids gave results of ≤2μg/ml MPL® and ≤0.1 – 1.4 QAU/ml IgE antigenicity, demonstrating approximately ≥96 & 99% adsorption respectively. Allergoid and MPL® adsorption in different MATA-MPL allergy immunotherapy formulations is consistent and meets guideline recommendations. MCT formulations treated to disrupt electrostatic, hydrophobic and ligand exchange interactions, gave an MPL® content of ≤2μg/ml in supernatant samples. MCT formulations treated to disrupt aromatic interactions, gave an MPL® content of 73–92μg/ml in supernatant samples. MPL® adsorption to L-tyrosine in MCT formulations is based on interactions between the 2-deoxy-2-aminoglucose backbone on MPL® and aromatic ring of L-tyrosine in MCT, such as C-H···π interaction. MCT could be an alternative adjuvant depot for some infectious disease antigens.
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      PubDate: 2015-08-18T04:14:04Z
       
  • Zinc(II) and copper(II) complexes with hydroxypyrone iron chelators
    • Abstract: Publication date: Available online 11 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Joanna Izabela Lachowicz, Valeria Marina Nurchi, Guido Crisponi, Maria de Guadalupe Jaraquemada-Pelaez, Małgorzata Ostrowska, Julia Jezierska, Elżbieta Gumienna-Kontecka, Massimiliano Peana, Maria Antonietta Zoroddu, Duane Choquesillo-Lazarte, Juan Niclós-Gutiérrez, Josefa Maria González-Pérez
      High stability of the complexes formed at physiological pH is one of the basic requisites that a good iron chelator must possess. At the same time the chelating agent must be selective toward iron, i.e. the stability of iron complexes must be significantly higher than that of the complexes formed with essential metal ions, in order that these last ones do not perturb iron chelation. In the frame of our research on iron chelators we have designed and synthesized a series of tetradentate derivatives of kojic acid, and examined their binding properties toward Fe3+ and Al3+. In this paper, for a characterization of the behavior of the proposed iron chelating agents in biological fluids, their complex formation equilibria with copper(II) and zinc(II) ions have been fully characterized together with a speciation study, showing the degree at which the iron chelators interfere with the homeostatic equilibria of these two essential metal ions.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Novel binuclear μ-oxo diruthenium complexes combined with ibuprofen
           and ketoprofen: interaction with relevant target biomolecules and
           anti-allergic potential
    • Abstract: Publication date: Available online 8 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Gabriela Campos Seuanes, Mariete Barbosa Moreira, Tânia Petta, Maria Perpétua Freire de Moraes Del Lama, Luiz Alberto Beraldo de Moraes, Anderson Rodrigo Moraes de Oliveira, Rose Mary Zumstein Georgetto Naal, Sofia Nikolaou
      This work presents the synthesis and characterization of two novel binuclear ruthenium compounds of general formula [Ru2O(carb)2(py)6](PF6)2, where py=pyridine and carb are the non-steroidal anti-inflammatory drugs ibuprofen (1) and ketoprofen (2). Both complexes were characterized by ESI-MS/MS spectrometry. The fragmentation patterns, which confirm the proposed structures, are presented. Besides that, compounds 1 and 2 present the charge transfer transitions within 325 – 330nm; and the intra-core transitions around 585nm, which is the typical spectra profile for [Ru2O] analogues. This suggests the carboxylate bridge has little influence in their electronic structure. The effects of the diruthenium complexes on Ig-E mediated mast cells activation were evaluated by measuring the enzyme β-hexosaminidase released by mast cells stimulated by antigen. The inhibitory potential of the ketoprofen complex against mast cell stimulation suggests its promising application as a therapeutic agent for treating or preventing IgE-mediated allergic diseases. In addition, in vitro metabolism assays had shown that the ibuprofen complex is metabolized by the cytochrome P450 enzymes.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Structure, physicochemical and biological properties of new complex salt
           of aqua-(nitrilotriacetato-N,O,O',O'')-oxidovanadium(IV) anion with
           1,10-phenanthrolinium cation
    • Abstract: Publication date: Available online 10 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): A. Tesmar, I. Inkielewicz-Stępniak, A. Sikorski, D. Wyrzykowski, D. Jacewicz, P. Zięba, J. Pranczk, T. Ossowski, L. Chmurzyński
      The crystal structure of new 1,10-phenathrolin-1-ium aqua-(nitrilotriacetato-N,O,O',O'')-oxidovanadium(IV) semihydrate of molecular formula (phenH)[VO(NTA)(H2O)]∙½H2O was determined. This is the first example of structurally characterized compound comprises a distinctly separated, monomeric [VO(NTA)(H2O)]− coordination entity. The crystallographic measurements have subsequently been complemented by the IR spectroscopic characterization and thermal analysis. Furthermore, the electrochemical (cyclic voltammetry) as well as spectrophotometric (UV–vis) studies revealed that the compound is capable to scavenge the superoxide free radicals (O2 •–) as well as stable organic radicals i.e. 2,2′-azinobis(3-ethylbenzothiazoline-6 sulfonic acid) cation radical (ABTS+•) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), but its reactivity towards radicals is lower than that of VOSO4. Finally, biological properties of the complex in the range of 1 – 100μM were investigated in relation to its cytoprotective activity against the oxidative damage generated exogenously by using hydrogen peroxide in the hippocampal neuronal HT22 cell line (the MTT and LDH tests). It has been established that in contrast to VOSO4 the title compound protects the HT22 from the oxidative damage. The paper presents a new perspective for oxidovanadium(IV) complexes as candidates for novel, low-molecular mass cytoprotective agents.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Differerent zinc(II) complex species and binding modes at Aβ
           N-terminus drive distinctlong range cross-talks in the Aβ monomers
    • Abstract: Publication date: Available online 10 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Adriana Pietropaolo, Cristina Satriano, Gaetano Strano, Diego La Mendola, Enrico Rizzarelli
      The present study addressess the reconstruction of the free-energy landscapes of Amyloid-Beta1-42 (Aβ42) coordinated respectively with one and two zinc ions, to scrutinize wheter different Aβ-zinc complex species, i.e., mononuclear and dinuclear metal complexes, induce different Aβ conformation features. We found a subtle switch of intramolecular interactions, depending both on the zinc coordination environment and on the peptide to zinc stoichiometric ratio. On the one side, hairpin-like structures are predominant in mononuclear complexes, where a salt-bridge that involves Lys28-Glu22 and Lys16-Asp23 is stabilized. On the other side, elongated conformations are instead stabilized in the dinuclear zinc complexes. Experimental studies of atomic force microscopy as well as of zinc-Aβ complex species distribution diagrams provide evidence that the theroretical calculations can be rationalized in terms of the correlation between the increased amount of amorphous aggregates and the Aβ/Zn2+ ratio.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Redox-implications associated with the formation of complexes between
           copper ions and reduced or oxidized glutathione
    • Abstract: Publication date: Available online 11 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Margarita E. Aliaga, Camilo López-Alarcón, Raquel Bridi, Hernán Speisky
      Binding of copper by reduced glutathione (GSH) is generally seen as a mechanism to lower, if not abolish, the otherwise high electrophilicity and redox activity of its free ions. In recent years, however, this concept has been contradicted by new evidence revealing that, rather than stabilizing free copper ions, its binding to GSH leads to the formation of a Cu(I)-[GSH]2 complex capable of reducing molecular oxygen into superoxide. It is now understood that, under conditions leading to the removal of such radicals, the Cu(I)-[GSH]2 complex is readily oxidized into Cu(II)-GSSG. Interestingly, in the presence of a GSH excess, the latter complex is able to regenerate the superoxide-generating capacity of the complex it originated from, opening the possibility that a GSH-dependent interplay exists between the reduced and the oxidized glutathione forms of these copper-complexes. Furthermore, recent evidence obtained from experiments conducted in non-cellular systems and intact mitochondria indicates that the Cu(II)-GSSG complex is also able to function in a catalytic manner as an efficient superoxide dismutating- and catalase-like molecule. Here we review and discuss the most relevant chemical and biological evidence on the formation of the Cu(I)-[GSH]2 and Cu(II)-GSSG complexes and on the potential redox implications associated with their intracellular occurrence.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Structure-Specific Adipogenic Capacity of Novel, Well-defined Ternary
           Zn(II)-Schiff Base Materials. Biomolecular Correlations in Zinc-Induced
           Differentiation of 3T3-L1 Pre-adipocytes to Adipocytes
    • Abstract: Publication date: Available online 11 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): O. Tsave, E. Halevas, M.P. Yavropoulou, A. Kosmidis Papadimitriou, J.G. Yovos, A. Hatzidimitriou, C. Gabriel, V. Psycharis, A. Salifoglou
      Among the various roles of zinc discovered to date, its exogenous activity as an insulin mimetic agent stands as a contemporary challenge currently under investigation and a goal to pursue in the form of a metallodrug against type 2 Diabetes mellitus. Poised to investigate the adipogenic potential of Zn(II) and appropriately configure its coordination sphere into well-defined anti-diabetic forms, a) a series of new well-defined ternary dinuclear Zn(II)-L (L=Schiff base ligands with a variable number of alcoholic moieties) compounds were synthesized and physicochemically characterized, c) their cytotoxicity and migration effect(s) in both pre- and mature adipocytes was assessed, d) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and d) closely linked molecular targets involving or influenced by the specific Zn(II) forms were perused through molecular biological techniques, cumulatively delineating factors involved in Zn(II)-induced adipogenesis. Collectively, the results a) reveal the significance of key structural features of Schiff ligands coordinated to Zn(II), thereby influencing its (a)toxicity behavior and insulin-like activity, b) project molecular targets influenced by the specific forms of Zn(II) formulating its adipogenic potential, and c) exemplify the interwoven relationship between Zn(II)-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine tuning structure-specific zinc-induced adipogenicity in future efficient antidiabetic drugs.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western
           blot analysis of ruthenium(II) polypyridyl complex against human lung
           decarcinoma A549 cell
    • Abstract: Publication date: Available online 12 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Shang-Hai Lai, Guang-Bin Jiang, Jun-Hua Yao, Wei Li, Bing-Jie Han, Cheng Zhang, Chuan-Chuan Zeng, Yun-Jun Liu
      A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2 Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6±0.4, 9.0±0.8, 1.5±0.2 and 1.5±0.3μM, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins.
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      PubDate: 2015-08-13T03:45:54Z
       
  • Functional fluorescent nonporous silica nanoparticles as carriers for
           Pt(IV) anticancer prodrugs
    • Abstract: Publication date: Available online 6 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Mauro Ravera, Elena Perin, Elisabetta Gabano, Ilaria Zanellato, Guido Panzarasa, Katia Sparnacci, Michele Laus, Domenico Osella
      Multilayer fluorescent nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were used as delivery systems for Pt(IV) candidate antitumor prodrugs. Spherical SNPs of three different sizes (diameter around 120, 100, and 50nm) were loaded with two different complexes, namely (OC-6-33)-diamminebis(4-carboxybutanoato)dichloridoplatinum(IV) (1) and (OC-6-44)-diammine(4-carboxybutanoato)dichloridoethanolatoplatinum(IV) (2), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic groups of the complexes. Complex 1 proved to cause heavy and irreversible agglomeration of SNPs; likely, the presence of two reactive carboxylic functionalities induces the formation of cross-links between the amino-decorated SNPs. On the contrary, the conjugates 2-SNP, obtained from the monofunctionalized 2, afforded aqueous nano-suspensions reasonably stable toward aggregation. These solutions showed a limited Pt release in water in the absence of any reducing agents, mainly in form of a Pt(IV) derivative generated by the hydrolysis of the Si-O-Si bond of the functionalized arms attached to silica. In the presence of ascorbic acid, the reduction Pt(IV)→Pt(II) caused the release of the active metabolite cisplatin. Conjugates 2-SNP exhibited much better antiproliferative activity on the Pt-sensitive ovarian A2780 cell line than parent cisplatin and free 2, due to their more efficient cellular uptake.
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      PubDate: 2015-08-09T03:36:59Z
       
  • Investigating the influence of histidine residues on the metal ion binding
           ability of the wheat metallothionein γ-Ec-1 domain
    • Abstract: Publication date: Available online 8 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Katsiaryna Tarasava, Eva Freisinger
      While Zn(II) and Cd(II) have similar geochemical and environmental properties, their biological properties are distinctively different as Cd(II) ions have very limited metabolic significance and are mostly even toxic, while Zn(II) ions belong to the most essential micronutrients. One of the key proteins involved in intracellular Zn(II) and Cd(II) binding are metallothioneins (MTs), small cysteine-rich proteins ubiquitously found in many different organisms. In the past two decades, also MT sequences from diverse species that contain histidine residues have been found, and His-metal ion coordination has been shown. It is not clear, however, why in some MTs part of the Cys residues are replaced by His, while most other MTs only contain Cys residues for metal ion binding. To address this question, we used the γ-domain of the early-cysteine labeled (Ec-1) metallothionein from common wheat as a model system because its enclosed M2Cys6 cluster represents the smallest metal-thiolate cluster possible with divalent metal ions. Based on the known three-dimensional structure of the γ-domain we set about to investigate the influence of a single Cys-to-His mutation on the structure and metal ion binding abilities of this domain. Combined data obtained by mass spectrometry, UV, as well as NMR spectroscopy suggest a preference for Zn(II) versus Cd(II) ions in the histidine containing binding site.


      PubDate: 2015-08-09T03:36:59Z
       
  • Insight into Structural Rearrangements and Interdomain Interactions
           Related to Electron Transfer between Flavin Mononucleotide and Heme in
           Nitric Oxide Synthase: A Molecular Dynamics Study
    • Abstract: Publication date: Available online 7 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yinghong Sheng, Linghao Zhong, Dahai Guo, Gavin Lau, Changjian Feng
      Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. A clear understanding of this large conformational change is critical, since this step is the rate-limiting in the NO production. In this study, molecular dynamics simulations were conducted on a model of an oxygenase/FMN (oxyFMN) construct of human inducible NOS (iNOS). This is to investigate the structural rearrangements and the domain interactions before and after the FMN−heme interdomain electron transfer (IET). We carried out simulations on the iNOS oxyFMN•CaM complex models in [Fe(III)][FMNH−] and [Fe(II)][FMNH•] oxidation states, the pre- and post-IET states. The comparison of the dynamics and conformations of the iNOS construct at the two oxidation states has allowed us to identify key factors related to facilitating the FMN−heme IET process. The computational results demonstrated that the conformational change is redox-dependent. Predictions of the key interacting sites in optimal interdomain FMN/heme docking are well supported by experimental data in the literature. An intra-subunit pivot region is predicted to modulate the FMN domain motion and correlate with existence of a bottleneck in the conformational sampling that leads to the electron transfer-competent state. Interactions of the residues identified in this work are proposed to ensure that the FMN domain moves with appropriate degrees of freedom and docks to proper positions at the heme domain, resulting in efficient IET and nitric oxide production. Synopsis Comparison of the dynamics and structures of an iNOS construct at two oxidation states identified key factors related to the FMN■heme interdomain electron transfer (IET) process. The computational results demonstrated that the FMN domain motion is redox dependent. Interactions of the residues identified in this work are proposed to ensure that the FMN domain moves with appropriate degree of freedom and docks to proper positions at the heme domain, resulting in efficient IET and NO production.
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      PubDate: 2015-08-09T03:36:59Z
       
  • Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II)
           complexes as topoisomerase IIa inhibitors
    • Abstract: Publication date: Available online 8 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Franco Bisceglie, Anastasia Musiari, Silvana Pinelli, Rossella Alinovi, Ilaria Menozzi, Eugenia Polverini, Pieralberto Tarasconi, Matteo Tavone, Giorgio Pelosi
      A series of quinoline-2-carboxaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes were synthesized and characterized. In all complexes the ligands are in the E configuration with respect to the imino bond and behave as terdentate. The copper(II) complexes form square planar derivatives with one molecule of terdentate ligand and chloride ion. A further non coordinated chloride ion compensate the overall charge. Nickel(II) ions form instead octahedral complexes with two ligands for each metal ion, independently from the stoichiometric metal:ligand ratio used in the synthesis. Ligands and complexes were tested for their antiproliferative properties on histiocytic lymphoma cell line U937. Copper(II) derivatives are systematically more active than the ligands and the nickel complexes. All copper derivatives result to inhibit topoisomerase IIa in vitro. Computational methods were used to propose a model to explain the different extent of inhibition presented by these compounds. The positive charge of the dissociated form of the copper complexes may play a key role in their action.
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      PubDate: 2015-08-09T03:36:59Z
       
  • Nanomolar aluminum induces expression of the inflammatory systemic
           biomarker C-reactive protein (CRP) in human brain microvessel endothelial
           cells (hBMECs)
    • Abstract: Publication date: Available online 1 August 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Peter N. Alexandrov, Theodore P.A. Kruck, Walter J. Lukiw
      C-reactive protein (CRP; also known as pentraxin 1, PTX1), a 224 amino acid soluble serum protein organized into a novel pentameric ring-shaped structure, is a highly sensitive pathogenic biomarker for systemic inflammation. High CRP levels are found in practically every known inflammatory state, and elevated CRP levels indicate an increased risk for several common age-related human degenerative disorders, including cardiovascular disease, cancer, diabetes, and Alzheimer's disease (AD). While the majority of CRP is synthesized in the liver for secretion into the systemic circulation, it has recently been discovered that an appreciable amount of CRP is synthesized in highly specialized endothelial cells that line the vasculature of the brain and central nervous system (CNS). These highly specialized cells, the major cell type lining the human CNS vasculature, are known as human brain microvessel endothelial cells (hBMECs). In the current pilot study we examined (i) CRP levels in human serum obtained from AD and age-matched control patients; and (ii) analyzed the effects of nanomolar aluminum sulfate on CRP expression in primary hBMECs. The three major findings in this short communication are: (i) that CRP is up-regulated in AD serum; (ii) that CRP serum levels increased in parallel with AD progression; and (iii) for the first time show that nanomolar aluminum potently up-regulates CRP expression in hBMECs to many times its 'basal abundance'. The results suggest that aluminum-induced CRP may in part contribute to a pathophysiological state associated with a chronic systemic inflammation of the human vasculature.
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      PubDate: 2015-08-05T03:33:30Z
       
  • Behavior of the potential antitumor VIVO complexes formed by flavonoid
           ligands. 2. Characterization of sulfonate derivatives of quercetin and
           morin, interaction with the bioligands of the plasma and preliminary
           biotransformation studies
    • Abstract: Publication date: Available online 31 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Daniele Sanna, Valeria Ugone, Luisa Pisano, Maria Serra, Giovanni Micera, Eugenio Garribba
      The biotransformation in the plasma and red blood cells of two potential antitumor VIVO complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5’-sulfonic acid or queS and morin-5’-sulfonic acid or morS) was studied by spectroscopic (EPR, Electron Paramagnetic Resonance) and computational (DFT, Density Functional Theory) methods. Que and queS form with VIVO stable complexes, and in the systems with apo-transferrin (apo-hTf) and albumin (HSA) VO(que)2 and VO(queS)2 remain unchanged. VO(mor)2 and VO(morS)2 undergo displacement reactions to give the partial formation of (VO) x (HSA) and (VO)(apo-hTf)/(VO)2(apo-hTf); moreover, morS forms with apo-transferrin and albumin mixed species VO–morS–apo-hTf and VO–morS–HSA. In the systems with apo-hTf and HSA anisotropic EPR spectra at room temperature are detected in which the protein is not directly coordinated to VIVO2+ ion. This is explained assuming that the bis-chelated complexes interact strongly with the proteins through a network of hydrogen bonds with the polar groups present on the protein surface. It is suggested that this “indirect” transport of VIVO species could be common to all the species containing ligands which can interact with the blood proteins. Uptake experiments by red blood cells were also carried out, using vanadium concentration of 5.0×10−4 M and incubation time in the range 0–160min. VO(que)2/VO(queS)2 and VO(mor)2/VO(morS)2 cross the erythrocytes membrane and in the cytosol VO(que)2/VO(queS)2 do not transform, whereas VO(mor)2/VO(morS)2 give the partial formation of mixed species with hemoglobin (Hb) and other VIVO species.
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      PubDate: 2015-07-31T21:07:04Z
       
  • The Homopentameric Chlorite Dismutase from Magnetospirillum sp.
    • Abstract: Publication date: Available online 15 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Diana M. Freire, Maria G. Rivas, André M. Dias, Ana T. Lopes, Cristina Costa, Teresa Santos-Silva, Sabine Van Doorslaer, Pablo J. González
      Chlorite dismutase (Cld) is a b-type heme containing enzyme that catalyzes the reduction of chlorite into chloride plus dioxygen. This enzyme has gained attention because it can be used in the development of bioremediation processes, biosensors, and controlled dioxygen production. In the present work, Cld was purified from Magnetospirillum sp. cells cultured anaerobically with acetate/perchlorate until stationary phase. Biochemical, spectroscopic and X-ray crystallography methods showed that Cld from Magnetospirillum sp. is a ~140kDa homopentamer comprising ~27.8kDa monomers. Preliminary X-ray crystallography studies confirmed the quaternary structure and the presence of one b-type heme per monomer. The EPR spectroscopic signature of the as-purified Cld samples is affected by the buffer composition used during the purification. Potassium phosphate buffer is the only buffer that affected neither the spectral nor the kinetic properties of Cld. Kinetic studies in solution revealed that Cld from Magnetospirillum sp. decomposes chlorite at high turnover rates with optimal pH6.0. A temperature below 10°C is required to avoid enzyme inactivation due to cofactor bleaching during turnover, and to achieve full substrate consumption. Cld kinetic parameters were not affected when kinetic assays were performed in presence of air or under argon atmosphere, but chloride is a weak mixed inhibitor that modifies the EPR signal of as-prepared samples.
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      PubDate: 2015-07-16T21:33:59Z
       
  • Phenylthiourea alters toxicity of mercury compounds in zebrafish larvae
    • Abstract: Publication date: Available online 14 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Tracy C. MacDonald, Susan Nehzati, Nicole J. Sylvain, Ashley K. James, Malgorzata Korbas, Sally Caine, Ingrid J. Pickering, Graham N. George, Patrick H. Krone
      In recent years larval stage zebrafish have been emerging as a standard vertebrate model in a number of fields, ranging from developmental biology to pharmacology and toxicology. The tyrosinase inhibitor 1-phenyl-2-thiourea (PTU) is used very widely with larval zebrafish to generate essentially transparent organisms through inhibition of melanogenesis, which has enabled many elegant studies in areas ranging from neurological development to cancer research. Here we show that PTU can have dramatic synergistic and antagonistic effects on the chemical toxicology of different mercury compounds. Our results indicate that extreme caution should be used when employing PTU in toxicological studies, particularly when studying toxic metal ions.
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      PubDate: 2015-07-16T21:33:59Z
       
  • Ru(II)-based complexes with
           N-(acyl)-N′,N′-(disubstituted)thiourea ligands: Synthesis,
           characterization, BSA- and DNA-binding studies of new cytotoxic agents
           against lung and prostate tumour cells
    • Abstract: Publication date: September 2015
      Source:Journal of Inorganic Biochemistry, Volume 150
      Author(s): Rodrigo S. Correa , Katia M. de Oliveira , Fábio G. Delolo , Anislay Alvarez , Raúl Mocelo , Ana M. Plutin , Marcia R. Cominetti , Eduardo E. Castellano , Alzir A. Batista
      Four ruthenium(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3–6.5×104 M−1, and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb=0.8–1.8×104 M−1) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.
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      PubDate: 2015-07-11T20:56:06Z
       
  • A molecular level mechanism for uranium (VI) toxicity through Ca2+
           displacement in pyrroloquinoline quinone-dependent bacterial dehydrogenase
           
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Katherine A. Burbank , Robert A. Walker , Brent M. Peyton
      Dipicolinic acid (DPA), a small molecule analogue for the pyrroloquinoline quinone (PQQ) bacterial dehydrogenase cofactor, was used to model displacement of the complexing ion, Ca2+, by a uranium (VI) dioxo-cation, UO2 2+ . Complexation of UO2 2+ with DPA through the displacement of Ca2+ was examined with UV/visible spectroscopy, ESI (electrospray ionization)-Mass spectrometry, and density functional theory based-modeling. The UO2 2+ displacement of other biologically important metal cations (Zn2+, Cu2+, Ni2+, and Fe3+) from DPA was also examined. Results show that UO2 2+ has a distinctly higher binding affinity (logβ=10.2±0.1) for DPA compared to that of Ca2+ (logβ=4.6±0.1), and provide molecular level insight into the mechanism of uranium toxicity associated with the {ONO} site. These results support those of VanEngelen et al. (2011) where a key interaction between PQQ and UO2 2+ produced significant uranium toxicity in bacteria. The observed toxicity mechanism was determined to be the displacement of a Ca2+ cation bound to the {ONO} site on PQQ and was observed even at submicromolar UO2 2+ concentrations. Here we couple experimental findings with density functional theory (DFT) calculations to investigate the electronic and structural properties that make the {ONO} site so distinctively favorable for UO2 2+ binding. This novel approach using integrated experimental and fundamental atomic based models opens the path to identify a library of potential uranium interactions with critical biological molecules.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Editorial Board
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Contents
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Metals in the active site of native protein phosphatase-1
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Ewald Heroes , Jens Rip , Monique Beullens , Luc Van Meervelt , Stefan De Gendt , Mathieu Bollen
      Protein phosphatase-1 (PP1) is a major protein Ser/Thr phosphatase in eukaryotic cells. Its activity depends on two metal ions in the catalytic site, which were identified as manganese in the bacterially expressed phosphatase. However, the identity of the metal ions in native PP1 is unknown. In this study, total reflection X-ray fluorescence (TXRF) was used to detect iron and zinc in PP1 that was purified from rabbit skeletal muscle. Metal exchange experiments confirmed that the distinct substrate specificity of recombinant and native PP1 is determined by the nature of their associated metals. We also found that the iron level associated with native PP1 is decreased by incubation with inhibitor-2, consistent with a function of inhibitor-2 as a PP1 chaperone.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Copper(II) complexes with the non-steroidal anti-inflammatory drug
           tolfenamic acid: Structure and biological features
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Alketa Tarushi , Spyros Perontsis , Antonios G. Hatzidimitriou , Athanasios N. Papadopoulos , Dimitris P. Kessissoglou , George Psomas
      Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf−1 and bipy led to the formation of [Cu(tolf-O,O′)(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O′)2(bipy)] (2), [Cu(tolf-O,O′)2(bipyam)]·0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O′)(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1–5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O′)4(DMF)2] (6).
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      PubDate: 2015-06-11T17:30:20Z
       
  • Synthesis, crystal structure and anaerobic DNA photocleavage of ruthenium
           complexes [Ru(tpy)(dpoq)Cl]+ and [Ru(tpy)(dpoq)CH3CN]2+
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Hui-juan Yu , Shu-mei Huang , Hui Chao , Liang-nian Ji
      Two new Ru(II) complexes [Ru(tpy)(dpoq)Cl]+ 1 and [Ru(tpy)(dpoq)CH3CN]2+ 2 (tpy=2,2':6',2''-terpyridine; dpoq=dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline) have been synthesized and characterized by elemental analysis, 1H NMR, electrospray ionization mass spectra (ESI-MS) and X-ray crystallographic study. The experimental results of spectra titration, thermal denaturation and viscosity measurements suggest that the two complexes intercalatively bind to DNA. When irradiated under light, the two complexes could efficiently photocleave DNA both under aerobic and anaerobic condition. The mechanism studies reveal that the photocleavage reaction functions through both oxygen-independent (photoinduced electron transfer, type III reaction) and oxygen-dependent (singlet oxygen generation, type II reaction) pathways and the oxygen-independent pathway is the major process. These complexes will be more promising photodynamic therapy (PDT) candidates used for treating hypoxic tumors.
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      PubDate: 2015-06-11T17:30:20Z
       
  • A novel resting form of the trinuclear copper center in the double mutant
           of a multicopper oxidase, CueO, Cys500Ser/Glu506Ala
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Takao Kajikawa , Ryosuke Sugiyama , Kunishige Kataoka , Takeshi Sakurai
      A multicopper oxidase, CueO was doubly mutated at its type I copper ligand, Cys500 and an acidic amino acid residue located in the proton transfer pathway, Glu506, to Ser and Ala, respectively. Cys500Ser/Glu506Ala was mainly in a novel resting form to afford the absorption band at ca. 400nm and an EPR signal with a highly anisotropic character derived from type III copper. However, Cys500Ser/Glu506Ala gave the same reaction intermediate (peroxide intermediate) as that from Cys500Ser and Cys500Ser/Glu506Gln.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Cis-[RuCl(BzCN)(N–N)(P–P)]PF6 complexes: Synthesis and in
           vitro antitumor activity (BzCN=benzonitrile;
           N–N=2,2′-bipyridine; 1,10-phenanthroline;
           P–P=1,4-bis(diphenylphosphino) butane,
           1,2-bis(diphenylphosphino)ethane, or
           1,1′-(diphenylphosphino)ferrocene)
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Flávia de C. Pereira , Benedicto A.V. Lima , Aliny P. de Lima , Wanessa C. Pires , Thallita Monteiro , Lorena F. Magalhães , Wanderson Costa , Angélica E. Graminha , Alzir A. Batista , Javier Ellena , Elisângela de P. Siveira-Lacerda
      The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN=benzonitrile; bipy=2,2′-bipyridine; phen=1,10-phenanthroline; dppe=1,2-bis(diphenylphosphino) ethane; dppb=1,4-bis-(diphenylphosphino)butane; dppf=1,1′-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)–(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02±8.21μM, while exhibiting lower cytotoxicity (IC50 =53.73±5.71μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Reactions of model proteins with aurothiomalate, a clinically established
           gold(I) drug: The comparison with auranofin
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Farivash Darabi , Tiziano Marzo , Lara Massai , Federica Scaletti , Elena Michelucci , Luigi Messori
      Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug that is currently being reconsidered as a candidate drug for cancer treatment and for other therapeutic indications within a more general drug repositioning program. As the biological effects of gold drugs seem to be mediated, mainly, by their interactions with protein targets we have analyzed here, in detail, the metalation patterns produced by aurothiomalate in a few model proteins. In particular, the reactions of aurothiomalate with the small proteins ribonuclease A, cytochrome c and lysozyme were explored through ESI MS (electrospray ionization mass spectrometry) analysis. Notably, characteristic and rather constant features emerged in the protein metalation patterns induced by AuTm that are markedly distinct from those caused by auranofin; a non-covalent interaction mode is invoked for AuTm binding to the mentioned proteins. The affinity constants of AuTm toward the three mentioned proteins were also initially assessed. The implications of the present findings are discussed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • HSA-based phosphorescent probe for two-photon in vitro visualization
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Pavel S. Chelushkin , Natalia V. Nukolova , Alexei S. Melnikov , Pavel Yu. Serdobintsev , Pavel A. Melnikov , Dmitry V. Krupenya , Igor O. Koshevoy , Sergey V. Burov , Sergey P. Tunik
      Two-photon microscopy reveals several advantages over conventional one since it provides higher spatial resolution as well as deeper penetration into the sample under study. The development of suitable two-photon probes is one of the most challenging tasks in this area. Here we present phosphorescent non-covalent adduct of human serum albumin and Au-Ag alkynyl-diphosphine complex, [Au14Ag4(C2Ph)12(PPh2C6H4PPh2)6][PF6]4, which exhibits high cross section of two-photon-induced luminescence (δ TPE) within large near-infrared excitation wavelength region (700–800nm) with maximum δ TPE about 38 GM at 740nm. This feature makes it a promising probe for multiphoton bioimaging as demonstrated by successful visualization of glioma C6 cells and various tissues by two-photon confocal microscopy both in planar and z-stacking modes. Additionally, the broad excitation region enables optimization of the signal-to-background auto-fluorescence ratio via variation of excitation wavelength.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Antitumor and antiparasitic activity of novel ruthenium compounds with
           polycyclic aromatic ligands
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Helena Guiset Miserachs , Micaella Cipriani , Jordi Grau , Marta Vilaseca , Julia Lorenzo , Andrea Medeiros , Marcelo A. Comini , Dinorah Gambino , Lucía Otero , Virtudes Moreno
      Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η6-p-cym)(L)][PF6], where p-cym=1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro- phenanthroline, 5. In the other two complexes, [RuCl2(η6-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonilanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower T. brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 =1.26±0.78μM) and antiparasitic (IC50 =0.19μM) agent, showing high selectivity towards the parasites (selectivity index>100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Molecular mechanisms of apoptosis and cell selectivity of zinc
           dithiocarbamates functionalized with hydroxyethyl substituents
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yee Seng Tan , Kah Kooi Ooi , Kok Pian Ang , Abdah Md Akim , Yoke-Kqueen Cheah , Siti Nadiah Abdul Halim , Hoi-Ling Seng , Edward R.T. Tiekink
      In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R=iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity was indicated with 2 being most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2–4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1–4 which is correlated with down-regulation of NF-ĸB.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Synthesis, crystal structure and biological activity of two Mn complexes
           with 4-acyl pyrazolone derivatives
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yue Li , Jing Zhao , Chuan-Chuan He , Li Zhang , Su-Rong Sun , Guan-Cheng Xu
      In order to study the biological activities of transitional metal complexes based on 4-acyl pyrazolone derivatives, two Mn complexes [Mn(HLa)(La)]·(CH3CN)1.5 ·H2O (1) and [Mn2(Lb)2(μ-EtO)2(EtOH)2] (2) (H2La =N-(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)-2- thiophenecarboxylic acid hydrazide, H2Lb =N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- 2-thiophenecarboxylic acid hydrazide) have been synthesized and characterized. Single crystal X-ray diffraction analysis indicated that 1 is a mononuclear complex and 2 exhibits a dinuclear centrosymmetric structure. Binding of the complexes with Herring Sperm DNA (HS-DNA) were showed that complexes 1 and 2 could intercalate to DNA with quenching constant of 5.3×104 M−1 and 4.9×104 M−1, respectively. The interactions of the complexes with bovine serum albumin (BSA) indicated complexes 1 and 2 could quench the intrinsic fluorescence of BSA in a static quenching process. Further, the inhibitory effects of the complexes on the cell population growth of the human esophageal cancer Eca-109 cells and the cervical cancer HeLa cells were determined by MTT assay, which indicated that both 1 and 2 significantly inhibited the growth of Eca-109 and HeLa cells, the inhibitory activity of complex 1 is stronger than that of 2. We further observed that complex 1 inhibited the growth of HeLa cells through inducing the apoptosis and arresting cell cycle at S phase. Our results suggested that both complexes 1 and 2 have DNA- and protein-binding capacity and antitumor activity.
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      PubDate: 2015-06-08T15:27:47Z
       
  • Synthesis, chemical characterization, computational studies and biological
           activity of new DNA methyltransferases (DNMTs) specific inhibitor.
           Epigenetic regulation as a new and potential approach to cancer therapy
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): C. Pellerito , O. Morana , F. Ferrante , G. Calvaruso , A. Notaro , S. Sabella , T. Fiore
      This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, 119Sn{1H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV–vis, fluorescence and 1H, 13C and 119Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probable stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 and Chang liver cells, an immortalized non-tumor hepatic cell line, have been investigated. The effect of a variation in structure of caf1 found to lead to a change in the respective antiproliferative properties: caf1 induces loss of viability in HCT116, MDA-MB-231, HepG2; the complex shows only moderate effects in non-tumor Chang liver cells. caf1 exerts lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with H3CAF modulates the marked cytotoxic activity exerted by Bu2SnCl2; caf1 displays a considerably more pronounced antitumoural effect towards cell lines than caffeic acid. It is known that caffeic acid can modulate DNA (cytosine-5)-methyltransferases 1 (DNMT1) mediated DNA methylation. In this paper we demonstrate that caf1 treatment was able to induce a time-dependent reduction of global DNA methylated status. This effect was also confirmed by a concomitant reduction DNMT1 expression level. The effect induced by caf1 was more evident not only respect to untreated cells but also compared to H3CAF treated cells.
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      PubDate: 2015-06-08T15:27:47Z
       
  • A versatile salicyl hydrazonic ligand and its metal complexes as antiviral
           agents
    • Abstract: Publication date: Available online 27 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): D. Rogolino , M. Carcelli , A. Bacchi , C. Compari , Laura Contardi , E. Fisicaro , A. Gatti , M. Sechi , A. Stevaert , L. Naesens
      Acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. In the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination can be a successful strategy to inhibit the activity of the metalloenzyme. As a part of this ongoing research, we synthesised the acylhydrazone H2L and its complexes with Mg(II), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). Their characterization, both in solution - also by means of potentiometric studies - and in the solid state, evidenced the ability of the o-vanillin hydrazone scaffold to give rise to different types of metal complexes, depending on the metal and the reaction conditions. Furthermore, we evaluated both the free ligand and its metal complexes in in vitro studies against a panel of diverse DNA- and RNA-viruses. In particular, the Mg(II), Mn(II), Ni(II) and Zn(II) complexes had EC50 values in the low micromolar range, with a pronounced activity against vaccinia virus.
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      PubDate: 2015-05-28T07:22:58Z
       
  • Cellular trafficking, accumulation and DNA platination of a series of
           cisplatin-based dicarboxylato Pt(IV) prodrugs
    • Abstract: Publication date: Available online 26 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Mauro Ravera , Elisabetta Gabano , Ilaria Zanellato , Ilaria Bonarrigo , Manuela Alessio , Fabio Arnesano , Angela Galliani , Giovanni Natile , Domenico Osella
      A series of Pt(IV) anticancer prodrug candidates, having the equatorial arrangement of cisplatin and bearing two aliphatic carboxylato axial ligands, has been investigated to prove the relationship between lipophilicity, cellular accumulation, DNA platination and antiproliferative activity on the cisplatin-sensitive A2780 ovarian cancer cell line. Unlike cisplatin, no facilitate influx/efflux mechanism appears to operate in the case of the Pt(IV) complexes under investigation, thus indicating that they enter by passive diffusion. While Pt(IV) complexes having lipophilicity comparable to that of cisplatin (negative values of log P o/w) exhibit a cellular accumulation similar to that of cisplatin, the most lipophilic complexes of the series show much higher cellular accumulation (stemming from enhanced passive diffusion), accompanied by greater DNA platination and cell growth inhibition. Even if the Pt(IV) complexes are removed from the culture medium in the recovery process, the level of DNA platination remains very high and persistent in time, indicating efficient storing of the complexes and poor detoxification efficiency.
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      PubDate: 2015-05-28T07:22:58Z
       
  • Reactivity of dinuclear copper(II) complexes towards melanoma cells:
           correlation with its stability, tyrosinase mimicking and nuclease activity
           
    • Abstract: Publication date: Available online 19 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Cléia Justino Nunes , Beatriz Essenfelder Borges , Lia Sumie Nakao , Eugénie Peyroux , Renaud Hardré , Bruno Faure , Marius Réglier , Michel Giorgi , Marcela Bach Prieto , Carla Columbano Oliveira , Ana M. Da Costa Ferreira
      In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species were very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Morever, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.
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      PubDate: 2015-05-23T07:09:57Z
       
  • Reduced accumulation of platinum drugs is not observed in drug-resistant
           ovarian cancer cell lines derived from cisplatin-treated patients
    • Abstract: Publication date: Available online 14 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Marina Stukova , Matthew D. Hall , Samantha D. Tsotsoros , James P. Madigan , Nicholas P. Farrell , Michael M. Gottesman
      The resistance of ovarian cancer towards front-line chemotherapy, usually cisplatin or carboplatin in combination with paclitaxel or docetaxel, remains a major clinical challenge. Resistance to these agents has been largely studied using cell lines selected for resistance to agents in vitro. We examined a series of paired cell lines derived from patients with ovarian cancer prior to chemotherapy (PEO1, PEO4, PEO14 and PEA1), and following the acquisition of resistance to a platinum-based chemotherapy regimen (PEO6, PEO23 and PEA2, respectively). All resistant patient lines showed resistance to cisplatin (2-5-fold), but this did not correspond with lowered accumulation. No general cross-resistance was observed for oxaliplatin, paclitaxel or docetaxel, and paclitaxel accumulation was not affected. PEO1 cells carrying BRCA2 mutations were hypersensitive to the PARP inhibitors olaparib and velaparib, but all other cell lines expressing functional forms of BRCA2 were less sensitive. While reduced drug accumulation was not observed, we believe these pairs of lines are of use to researchers studying Pt drug resistance and experimental therapeutics against drug-resistant ovarian cancer.
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      PubDate: 2015-05-18T17:32:13Z
       
  • Oxidovanadium(IV) Sulfate-induced Glucose Uptake in HepG2 Cells through
           IR/Akt Pathway and Hydroxyl Radicals
    • Abstract: Publication date: Available online 15 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Qian Zhao , Deliang Chen , Pingsheng Liu , Taotao Wei , Fang Zhang , Wenjun Ding
      The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5-50 μM) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (·OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced ·OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway.
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      PubDate: 2015-05-18T17:32:13Z
       
  • Synthesis, crystal structure and investigation of mononuclear copper(II)
           and zinc(II) complexes of a new carboxylate rich tripodal ligand and their
           interaction with carbohydrates in alkaline aqueous solution
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Christopher D. Stewart , Mayra Pedraza , Hadi Arman , Hua-Jun Fan , Eduardo Luiz Schilling , Bruno Szpoganicz , Ghezai T. Musie
      A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N-[carboxymethyl]-β-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di-zinc(II), ((CH3)4 N)2[2]2, complexes have been synthesized as carbohydrate binding models in aqueous solutions. The ligand and complexes have been fully characterized using several techniques, including single crystal X-ray diffraction. The interactions of (NH4)2[1]2 and ((CH3)4 N)2[2]2 with d-glucose, d-mannose, d-xylose and xylitol in aqueous alkaline media were investigated using UV–Vis and 13C-NMR spectroscopic techniques, respectively. The molar conductance, NMR and ESI–MS studies indicate that the complexes dissociate in solution to produce the respective complex anions, 1 − and 2 −. Complexes 1 − and 2 − showed chelating ability towards the naturally abundant and biologically relevant sugars, d-glucose, d-mannose, d-xylose, and xylitol. The complex ions bind to one molar equivalent of the sugars, even in the presence of stoichiometric excess of the substrates, in solution. Experimentally obtained spectroscopic data and computational results suggest that the substrates bind to the metal center in a bidentate fashion. Apparent binding constant values, pK app, between the complexes and the substrates were determined and a specific mode of substrate binding is proposed. The pK app and relativistic density functional theory (DFT) calculated Gibbs free energy values indicate that d-mannose displayed the strongest interaction with the complexes. Syntheses, characterizations, detailed substrate binding studies using spectroscopic techniques, single crystal X-ray diffraction and geometry optimizations of the complex-substrates with DFT calculations are also reported.
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      PubDate: 2015-05-18T17:32:13Z
       
  • Insights into the mechanisms underlying the antitumor activity of an
           oxidovanadium(IV) compound with the antioxidant naringenin. Albumin
           binding studies
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): María S. Islas , Luciana G. Naso , Luis Lezama , María Valcarcel , Clarisa Salado , Meritxell Roura-Ferrer , Evelina G. Ferrer , Patricia A.M. Williams
      Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of tomatoes showed low antioxidant properties among other flavonoids due to its structural characteristics. Since many flavonoids were shown to have cell-killing and antioxidant activities, naringenin was investigated herein. In parallel with its antioxidant activities the flavonoid showed very low cytotoxicity at concentrations up to 100μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines. Furthermore, a newly-synthesized and characterized complex of naringenin and oxidovanadium(IV) ([VIVO(nar)2]·2H2O, VOnar, with weak ferromagnetic coupling) was also studied. As a result, VOnar acted as a better compound on cell-killing and antioxidant activities (in vitro) than naringenin. The anti-proliferative effect of VOnar was accompanied by reactive oxygen species (ROS) generation, cell membrane and DNA damages, cell cycle arrest, caspase 3/7 activation and mitochondrial potential reduction. The higher parameters observed for the MDAMB231 cell line have been related to its low glutathione (GSH) content. The assays of the interaction of bovine serum albumin (BSA) with the complex showed the affinity of protein toward it and that there is only one binding site on the BSA molecule. However, metal complexation decreased the binding affinity to BSA of naringenin probably due to a steric hindrance of the complex.
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      PubDate: 2015-05-18T17:32:13Z
       
  • Inhibitory effects of nitrite on the reactions of bovine carbonic
           anhydrase II with CO2 and bicarbonate consistent with zinc-bound nitrite
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Per M. Nielsen , Angela Fago
      Carbonic anhydrase (CA) is a zinc enzyme that catalyzes hydration of carbon dioxide (CO2) and dehydration of bicarbonate in red blood cells, thus facilitating CO2 transport and excretion. Bovine CA II may also react with nitrite to generate nitric oxide, although nitrite is a known inhibitor of the CO2 hydration reaction. To address the potential in vivo interference of these reactions and the nature of nitrite binding to the enzyme, we here investigate the inhibitory effect of 10–30mM nitrite on Michaelis–Menten kinetics of CO2 hydration and bicarbonate dehydration by stopped-flow spectroscopy. Our data show that nitrite significantly affects the apparent dissociation constant K M for CO2 (11mM) and bicarbonate (221mM), and the turnover number k cat for the CO2 hydration (1.467×106 s−1) but not for the bicarbonate dehydration (7.927×105 s−1). These effects demonstrate mixed and competitive inhibition for the reaction with CO2 and bicarbonate, respectively, and are consistent with nitrite binding to the active site zinc. The high apparent dissociation constant found here for CO2, bicarbonate and nitrite (16–120mM) are all overall consistent with published data and reveal a large capacity of free enzyme available for binding each of the three substrates at their in vivo levels, with little or no significant interference among reactions. The low affinity of the enzyme for nitrite suggests that the in vivo interaction between red blood cell CA II and nitrite requires compartmentalization at the anion exchanger protein of the red cell membrane to be physiologically relevant.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
 
 
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