for Journals by Title or ISSN
for Articles by Keywords
help
  Subjects -> CHEMISTRY (Total: 846 journals)
    - ANALYTICAL CHEMISTRY (47 journals)
    - CHEMISTRY (597 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (26 journals)
    - INORGANIC CHEMISTRY (42 journals)
    - ORGANIC CHEMISTRY (45 journals)
    - PHYSICAL CHEMISTRY (67 journals)

INORGANIC CHEMISTRY (42 journals)

Showing 1 - 0 of 0 Journals sorted alphabetically
Acta Polymerica     Hybrid Journal   (Followers: 7)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Polymer Technology     Hybrid Journal   (Followers: 12)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 8)
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: 40)
Heterocyclic Communications     Hybrid Journal  
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 7)
Inorganic Chemistry     Full-text available via subscription   (Followers: 20)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 9)
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: 6)
Inorganics     Open Access  
International Journal of Bio-Inorganic Hybrid Nanomaterials     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: 6)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Inorganic Chemistry     Open Access   (Followers: 3)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 8)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 1)
Journal of Separation Science     Hybrid Journal   (Followers: 11)
Metallodrugs     Open Access   (Followers: 1)
Open Journal of Inorganic Chemistry     Open Access   (Followers: 2)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 13)
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: 2)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover Journal of Inorganic Biochemistry
  [SJR: 0.96]   [H-I: 87]   [3 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [2970 journals]
  • Characterization of the full-length btuB riboswitch from Klebsiella
           pneumoniae
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): J. Palou-Mir, A. Musiari, R.K.O. Sigel, M. Barceló-Oliver
      Riboswitches are cis-regulatory RNA elements on the mRNA level that control the expression of the downstream coding region. The interaction of the riboswitch with its specific metabolite, which is related to the function of the controlled gene, induces a structural change of the RNA architecture. Consequently, gene regulation is induced by un/masking of the ribosome binding site (RBS). In the genome of Klebsiella pneumoniae a sequence was identified by bioinformatics and proposed to be a B12 riboswitch regulated by coenzyme B12. Here we study this new coenzyme B12-dependent riboswitch system by in-line probing and ITC. The riboswitch sequence includes the whole expression platform as well as RBS. In-line probing experiments were performed to investigate the structural rearrangement of this 243-nt long RNA sequence while Isothermal Titration Calorimetry (ITC) yielded the thermodynamic parameters of the interaction between the riboswitch and its metabolite. The interaction of coenzyme B12 with the butB riboswitch of K. pneumoniae is an exothermic process with a 1:1 binding stoichiometry and binding affinities of log K A =6.73±0.02 at 15°C and log K A =6.00±0.09 at 30°C.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Cytotoxicity-boosting of kiteplatin by Pt(IV) prodrugs with axial benzoate
           ligands
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Nicola Margiotta, Salvatore Savino, Cristina Marzano, Concetta Pacifico, James D. Hoeschele, Valentina Gandin, Giovanni Natile
      Kiteplatin, the neglected drug analogous of cisplatin but containing cis-1,4-DACH in place of the two ammines, has been recently reevaluated for its activity against cisplatin- and oxaliplatin-resistant tumors, in particular colo-rectal cancer. With the aim of further improving the pharmacological activity of this drug, Pt(IV) prodrugs were derived by addition of two, differently substituted, benzoate groups in axial positions (X-ray structure). The cytotoxic activity of both compounds resulted markedly potentiated reaching nanomolar concentration against a wide panel of human cancer cells. The ability of benzoate ligands to enhance the activity of kiteplatin most likely originates from their lipophilicity promoting a higher drug accumulation in cancer cells; however, it is to be noted that the increase in pharmacological effect is far greater than the increase in cellular uptake. Overcoming cisplatin- and oxaliplatin-resistance by kiteplatin derivatives appears to relate to the inability of membrane extrusion pumps to remove active Pt species from tumor cells.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Synthesis, characterization and biological evaluation of
           99mTc/Re–tricarbonyl quinolone complexes
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Theocharis E. Kydonaki, Evangelos Tsoukas, Filipa Mendes, Antonios G. Hatzidimitriou, António Paulo, Lefkothea C. Papadopoulou, Dionysia Papagiannopoulou, George Psomas
      New rhenium(I) tricarbonyl complexes with the quinolone antimicrobial agents oxolinic acid (Hoxo) and enrofloxacin (Herx) and containing methanol, triphenylphosphine (PPh3) or imidazole (im) as unidentate co-ligands, were synthesized and characterized. The crystal structure of complex [Re(CO)3(oxo)(PPh3)]∙0.5MeOH was determined by X–ray crystallography. The deprotonated quinolone ligands are bound bidentately to rhenium(I) ion through the pyridone oxygen and a carboxylate oxygen. The binding of the rhenium complexes to calf-thymus DNA (CT DNA) was monitored by UV spectroscopy, viscosity measurements and competitive studies with ethidium bromide; intercalation was suggested as the most possible mode and the DNA-binding constants of the complexes were calculated. The rhenium complex [Re(CO)3(erx)(im)] was assayed for its topoisomerase IIα inhibition activity and was found to be active at 100μM concentration. The interaction of the rhenium complexes with human or bovine serum albumin was investigated by fluorescence emission spectroscopy (through the tryptophan quenching) and the corresponding binding constants were determined. The tracer complex [99mTc(CO)3(erx)(im)] was synthesized and identified by comparative HPLC analysis with the rhenium analog. The 99mTc complex was found to be stable in solution. Upon injection in healthy mice, fast tissue clearance of the 99mTc complex was observed, while both renal and hepatobiliary excretion took place. Preliminary studies in human K-562 erythroleukemia cells showed cellular uptake of the 99mTc tracer with distribution primarily in the cytoplasm and the mitochondria and less in the nucleus. These preliminary results indicate that the quinolone 99mTc/Re complexes show promise to be further evaluated as imaging or therapeutic agents.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Interactions of two cytotoxic organoruthenium(II) complexes with
           G-quadruplex
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Sara Seršen, Primož Šket, Janez Plavec, Iztok Turel
      Two previously isolated cytotoxic complexes [(η6-p-cymene)Ru(κ2-CF3COCHCOC5H3O)L]n+ (L=Cl (1); n=0, pta (2) (pta=1,3,5-triaza-7-phosphaadamantane); n=1) were investigated for their selectivity and ability to interact with DNA G-quadruplex adopted by d[G3ATG3ACACAG4ACG3] (3) whose topology exhibits diagonal, edge-type and double-chain reversal loops. Structural changes were followed using high-resolution NMR techniques in the presence of 1 and 2. Results showed weak interaction between the organoruthenium complexes and G-quadruplex. Moreover, no significant changes in thermal stability were confirmed by a UV-melting assay for both 1 and 2. These findings emphasize that anticancer activity of Ru(II) complexes may not be correlated with binding to nucleic acid like G-quadruplex.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • The inhibition of glycerol permeation through aquaglyceroporin-3 induced
           by mercury(II): A molecular dynamics study
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Angelo Spinello, Andreia de Almeida, Angela Casini, Giampaolo Barone
      Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200ns in the presence of Hg2+ ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg2+ ions covalently bound to Cys40 leads to a collapse of the aromatic/arginine selectivity filter (ar/R SF), blocking the passage of both glycerol and water. Interestingly, the local conformational changes of the protein follow mercury coordination by water and by aminoacidic donor atoms. Overall, the obtained results are important to improve the design of selective AQP inhibitors for future therapeutic and imaging applications.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Editorial Board
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160




      PubDate: 2016-06-17T18:00:43Z
       
  • Contents
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160




      PubDate: 2016-06-17T18:00:43Z
       
  • How half sandwich ruthenium compounds interact with DNA while not being
           hydrolyzed; a comparative study
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Theodoros Tsolis, Konstantinos D. Papavasileiou, Spyridon A. Divanis, Vasilios S. Melissas, Achilleas Garoufis

      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Inhibition of adhesion, migration and of α5β1 integrin in the
           HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Chiara Pelillo, Hilaria Mollica, Johannes A. Eble, Julius Grosche, Lea Herzog, Barbara Codan, Gianni Sava, Alberta Bergamo
      NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium-based drug characterised by the selective activity against tumour metastases. Previously we have shown the influence of the hepatic microenvironment to direct the arrest of the metastatic cells of colorectal cancer. Here we used the experimental model of HCT-116 colorectal cancer cells in vitro to explore whether the interference with α5β1 integrin may mechanistically explain the anti-metastatic effect of NAMI-A. NAMI-A inhibits two important steps of the tumour metastatic progression of colorectal cancer, i.e. the adhesion and migration of the tumour cells on the extracellular matrix proteins. The fibronectin receptor α5β1 integrin is likely involved in the anti-adhesive effects of NAMI-A on the HCT-116 colorectal cancer cells during their interaction with the extracellular matrix. Mechanistically, NAMI-A decreases the α5β1 integrin expression, and reduces FAK (Focal Adhesion Kinase) auto-phosphorylation on Tyr397, an important signalling event, involved in α5β1 integrin activation. These effects were validated by siRNA-induced knock down of the α5 integrin subunit and/or by the use of specific blocking mAbs against the active site of the integrin. Our results demonstrate the relevance of α5β1 integrin for colorectal cancer. We also show that the anti-metastatic effect of NAMI-A depends on the modulation of this integrin. Thus, our data on NAMI-A support the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • 4-Azidobenzyl ferrocenylcarbamate as an anticancer prodrug activated under
           reductive conditions
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Elisa Kinski, Paul Marzenell, Walter Hofer, Helen Hagen, Jevgenij A. Raskatov, Karl X. Knaup, Eva M. Zolnhofer, Karsten Meyer, Andriy Mokhir
      Aminoferrocene-based prodrugs are activated in the presence of cancer-specific amounts of reactive oxygen species, e.g. H2O2, with the formation of products of two types: Fe-containing complexes, which catalyze generation of HO and O2 −, and quinone methides, which alkylate glutathione and inhibit the antioxidative system of the cell. Both processes act synergistically by increasing the oxidative stress in cancer cells thereby leading to their death. However, in the activation step including the cleavage of a B–C bond one molecule of H2O2 is consumed that counteracts the desired effect of the products released from aminoferrocenes. We replaced an H2O2-sensitive trigger in original prodrugs with an azide group. This trigger is slowly reduced in the presence of glutathione with the formation of an unstable arylamine intermediate, which decomposes with the release of iron ions and iminoquinone methides. These products induce strong oxidative stress in cells as we confirmed using 2′,7′-dichlorodihydrofluorescin diacetate reagent in combination with flow cytometry. In this case the activation process does not consume H2O2. Correspondingly, we observed that the azide-containing prodrug is substantially more toxic towards human promyelocytic leukemia cell line HL-60 (IC50 =27±4μM) than its H2O2-responsive analogue (IC50 >50μM).
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • A novel dual-functioning ruthenium(II)–arene complex of an
           anti-microbial ciprofloxacin derivative — Anti-proliferative and
           anti-microbial activity
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Ziga Ude, Isolda Romero-Canelón, Brendan Twamley, Deirdre Fitzgerald Hughes, Peter J. Sadler, Celine J. Marmion
      7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η6-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral ‘piano-stool’ geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • A combined crystallographic analysis and ab initio calculations to
           interpret the reactivity of functionalized hexavanadates and their
           inhibitor potency toward Na+/K+-ATPase
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Xiao Xu, Nada Bošnjaković-Pavlović, Mirjana B. Čolović, Danijela Z. Krstić, Vesna M. Vasić, Jean-Michel Gillet, Pingfan Wu, Yongge Wei, Anne Spasojević-de Biré
      In vitro influence of five synthesized functionalized hexavanadates (V6) on commercial porcine cerebral cortex Na+/K+-ATPase activity has been studied. Dose dependent Na+/K+-ATPase inhibition was obtained for all investigated compounds. Calculated half maximal inhibitory concentration IC50 values, in mol/L, for Na+/K+-ATPase were 7.6×10−5, 1.8×10−5, 2.9×10−5, 5.5×10−5 for functionalized hexavanadates (V6) with tetrabutylammonium (TBA) [V6–CH3][TBA]2, [V6–NO2][TBA]2, [V6–OH][TBA]2 and [V6–C3][TBA]2 respectively. [V6–OH][Na]2 inhibited Na+/K+-ATPase activity up to 30% at maximal investigated concentration 1×10−3 mol/L. This reactivity has been interpreted using a study of the non-covalent interactions of functionalized hexavanadate hybrids through Cambridge Structural Database (CSD) analysis. Bibliographic searching has led to 18 different structures and 99 contacts. We have observed that C–H⋯O contacts consolidate the structures. We have also performed density functional theory (DFT) calculations and have determined electrostatic potential values at the molecular surface on a series of functionalized V6. These results enlightened their chemical reactivity and their potential biological applications such as the inhibition of the ATPase.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Behavior of the potential antitumor VIVO complexes formed by flavonoid
           ligands. 3. Antioxidant properties and radical production capability
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Daniele Sanna, Valeria Ugone, Angela Fadda, Giovanni Micera, Eugenio Garribba
      The radical production capability and the antioxidant properties of some VIVO complexes formed by flavonoid ligands were examined. In particular, the bis-chelated species of quercetin (que), [VO(que)2]2−, and morin (mor), [VO(mor)2], were evaluated for their capability to reduce the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and produce the hydroxyl radical •OH by Fenton-like reactions, where the reducing agent is VIVO2+. The results were compared with those displayed by other VIVO complexes, such as [VO(H2O)5]2+, [VO(acac)2] (acac=acetylacetonate) and [VO(cat)2]2− (cat=catecholate). The capability of the VIVO flavonoids complexes to reduce DPPH is much larger than that of the VIVO species formed by non-antioxidant ligands and it is due mainly to the flavonoid molecule. Through the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trapping assay of the hydroxyl radical it was possible to demonstrate that in acidic solution VIVO2+ has an effectiveness in producing •OH radicals comparable to that of Fe2+. When VIVO complexes of flavonoids were taken into account, the amount of hydroxyl radicals produced in Fenton-like reactions depends on the specific structure of the ligand and on their capability to reduce H2O2 to give •OH. Both the formation of reactive oxygen species (ROS) under physiological conditions by VIVO complexes of flavonoid ligands and their radical scavenging capability can be put in relationship with their antitumor effectiveness and it could be possible to modulate these actions by changing the features of the flavonoid coordinated to the VIVO2+ ion, such as the entity, nature and position of the substituents and the number of phenolic groups.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Editorial Board
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161




      PubDate: 2016-06-17T18:00:43Z
       
  • Elucidating the reactivity of Pt(II) complexes with (O,S) bidentate
           ligands towards DNA model systems
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Carolin Mügge, Domenica Musumeci, Elena Michelucci, Francesca Porru, Tiziano Marzo, Lara Massai, Luigi Messori, Wolfgang Weigand, Daniela Montesarchio
      In the search for novel platinum-based anticancer therapeutic agents, we have recently established a structural motif of (O,S) bidentate ligands bound to a Pt(II) metal center which is effective against various cancer cell lines. Aiming at further enhancing the cytotoxicity of metal-based drugs, the identification of potential biological targets and elucidation of the mode of action of selected lead compounds is of utmost importance. Here we report our studies on the DNA interaction of three representative Pt(II) complexes of the investigated series, using various model systems and analytical techniques. In detail, CD spectroscopy as well as ESI-MS and MS2 techniques were applied to gain an overall picture of the binding properties of this class of (O,S) bidentate Pt(II) compounds with defined oligonucleotide sequences in single strand, duplex or G-quadruplex form, as well as with the nucleobase 9-methylguanine. On the whole, it was demonstrated that the tested compounds interact with DNA and produce conformational changes of different extents depending on the sequence and structure of the examined oligonucleotide. Guanine was established as the preferential target within the DNA sequence, but in the absence or unavailability of guanines, alternative binding sites can be addressed. The implications of these results are thoroughly discussed.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Synthesis, characterization and biological evaluation of a 67Ga-labeled
           (η6-Tyr)Ru(η5-Cp) peptide complex with the HAV motif
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Zsolt Bihari, Filipe Vultos, Célia Fernandes, Lurdes Gano, Isabel Santos, João D.G. Correia, Péter Buglyó
      Heterobimetallic complexes with the evolutionary, well-preserved, histidyl-alanyl-valinyl (HAV) sequence for cadherin targeting, an organometallic Ru core with anticancer activity and a radioactive moiety for imaging may hold potential as theranostic agents for cancer. Visible-light irradiation of the HAVAY-NH2 pentapeptide in the presence of [(η5-Cp)Ru(η6-naphthalene)]+ resulted in the formation of a full sandwich type complex, (η6-Tyr-RuCp)-HAVAY-NH2 in aqueous solution, where the metal ion is connected to the Tyr (Y) unit of the peptide. Conjugation of this complex to 2,2′-(7-(1-carboxy-4-((4-isothiocyanatobenzyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-GA) and subsequent metalation of the resulting product with stable (natGa) and radioactive (67Ga) isotope yielded natGa/67Ga-NODA-GA-[(η6-Tyr-RuCp)-HAVAY-NH2]. The non-radioactive compounds were characterized by NMR spectroscopy and Mass Spectrometry. The cellular uptake and cytotoxicity of the radioactive and non-radioactive complexes, respectively, were evaluated in various human cancer cell lines characterized by different levels of N- or E-cadherins expression. Results from these studies indicate moderate cellular uptake of the radioactive complexes. However, the inhibition of the cell proliferation was not relevant.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Synthesis of novel Iron(III) chelators based on triaza macrocycle backbone
           and 1-hydroxy-2(H)-pyridin-2-one coordinating groups and their evaluation
           as antimicrobial agents
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): David G. Workman, Michael Hunter, Lynn G. Dover, David Tétard
      Several novel chelators based on 1-hydroxy-2(1H)-pyridinone coordinating groups decorating a triaza macrocyclic backbone scaffold were synthesised as potential powerful Fe3+ chelators capable of competing with bacterial siderophores. In particular, a novel chloromethyl derivative of 1-hydroxy-2(1H)-pyridinone exploiting a novel protective group for this family of coordinating groups was developed. These are the first examples of hexadentate chelators based on 1-hydroxy-2(1H)-pyridinone to be shown to have a biostatic activity against a range of pathogenic bacteria. Their efficacy as biostatic agents was assessed revealing that minor variations in the structure of the chelator can affect efficacy profoundly. The minimal inhibitory concentrations of our best tested novel chelators approach or are comparable to those for 1,4,7-tris(3-hydroxy-6-methyl-2-pyridylmethyl)-1,4,7-triazacyclononane, the best Fe3+ chelator known to date. The retarding effect these chelators have on microbial growth suggests that they could have a potential application as a co-active alongside antibiotics in the fight against infections.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Preface for the COST Action Special Issue
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Elisa Barea, Jens Müller



      PubDate: 2016-06-17T18:00:43Z
       
  • Differences in protein binding and excretion of Triapine and its Fe(III)
           complex
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Karla Pelivan, Walter Miklos, Sushilla van Schoonhoven, Gunda Koellensperger, Lars Gille, Walter Berger, Petra Heffeter, Christian R. Kowol, Bernhard K. Keppler
      Triapine has been investigated as anticancer drug in multiple clinical phase I/II trials. Although promising anti-leukemic activity was observed, Triapine was ineffective against solid tumors. The reasons are currently widely unknown. The biological activity of Triapine is strongly connected to its iron complex (Fe-Triapine) which is pharmacologically not investigated. Here, novel analytical tools for Triapine and Fe-Triapine were developed and applied for cell extracts and body fluids of treated mice. Triapine and its iron complex showed a completely different behavior: for Triapine, low protein binding was observed in contrast to fast protein adduct formation of Fe-Triapine. Notably, both drugs were rapidly cleared from the body (serum half-life time <1h). Remarkably, in contrast to Triapine, where (in accordance to clinical data) basically no renal excretion was found, the iron complex was effectively excreted via urine. Moreover, no Fe-Triapine was detected in serum or cytosolic extracts after Triapine treatment. Taken together, our study will help to further understand the biological behavior of Triapine and its Fe-complex and allow the development of novel thiosemicarbazones with pronounced activity against solid tumor types.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine
           phosphorylation but not activation
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Wei-Chih Kan, Te-Ling Lu, Pin Ling, Te-Hsiu Lee, Chien-Yu Cho, Chi-Ying F. Huang, Wen-Yih Jeng, Yui-Ping Weng, Chun-Yen Chiang, Jin Bin Wu, Te-Jung Lu
      The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Deferoxamine-induced increase in the intracellular iron levels in highly
           aggressive breast cancer cells leads to increased cell migration by
           enhancing TNF-α-dependent NF-κB signaling and TGF-β
           signaling
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Ping Liu, Kun He, Hongjiao Song, Zhufeng Ma, Weihai Yin, Lisa X. Xu
      Recent studies have suggested that excess iron accumulation may be a risk factor for breast cancer. However the role of iron in breast cancer metastasis has remained unclear. The major goal of our study is to investigate the roles of iron in breast cancer metastasis. We modulated the intracellular iron levels of human breast cancer cells, including the aggressive MDA-MB-231 cells and non-aggressive MCF-7 cells, by using Deferoxamine (DFO) – a most widely used iron chelator. We found that DFO treatment could deplete intracellular iron in MCF-7 cells. In contrast, DFO treatment led to a significant increase in the intracellular iron level in MDA-MB-231 cells. The MDA-MB-231 cells with the increased intracellular iron level exhibited increases in both mesenchymal markers and cell migration. Furthermore, the DFO-treated MDA-MB-231 cells showed increases in both tumor necrosis factor α (TNF-α)-induced nuclear factor kappa B (NF-κB) signaling and transforming growth factor-β (TGF-β) signaling, which could contribute to the enhanced cell migration. Collectively, our study has provided the first evidence suggesting that increased intracellular iron levels could lead to enhanced migration of aggressive breast cancer cells by increasing TNF-α-dependent NF-κB signaling and TGF-β signaling. Our study has also suggested that caution should be taken when DFO is applied for treating breast cancer cells, since DFO could produce differential effects on the intracellular iron levels for aggressive breast cancer cells and non-aggressive breast cancer cells.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Influence of chelation strength and bacterial uptake of gallium
           salicylidene acylhydrazide on biofilm formation and virulence of
           Pseudomonas aeruginosa
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Shoghik Hakobyan, Olena Rzhepishevska, Erik Björn, Jean-François Boily, Madeleine Ramstedt
      Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N′-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Binding properties of ruthenium(II) complexes [Ru(bpy)2(ppn)]2+ and
           [Ru(phen)2(ppn)]2+ with triplex RNA: As molecular “light
           switches” and stabilizers for poly(U)·poly(A)*poly(U) triplex
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Jia Li, Yanmei Sun, Zhiyuan Zhu, Hong Zhao, Lifeng Tan
      Stable RNA triplexes play key roles in many biological processes, while triplexes are thermodynamically less stable than the corresponding duplexes due to the Hoogsteen base pairing. To understand the factors affecting the stabilization of RNA triplexes by octahedral ruthenium(II) complexes, the binding of [Ru(bpy)2(ppn)]2+ (1, bpy=2,2′-bipyridine, ppn=2,4-diaminopyrimido[5,6-b]dipyrido[2,3-f:2′,3′-h]quinoxaline) and [Ru(phen)2(ppn)]2+ (2, phen=1,10-phenanthroline) to poly(U)·poly(A)*poly(U) (· denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing) has been investigated. The main results obtained here suggest that complexes 1 and 2 can serve as molecular “light switches” and stabilizers for poly(U)·poly(A)*poly(U), while the effectiveness of complex 2 are more marked, suggesting that the hydrophobicity of ancillary ligands has a significant effect on the two Ru(II) complexes binding to poly(U)·poly(A)*poly(U). This study further advances our knowledge on the binding of RNA triplexes with metal complexes, particularly with octahedral ruthenium polypyridyl complexes.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes
           (PTA=1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties
           
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): F. Battistin, F. Scaletti, G. Balducci, S. Pillozzi, A. Arcangeli, L. Messori, E. Alessio
      Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA=1,3,5-triaza-7-phosphaadamantane, X=Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH=PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind=indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1–5 in water and in physiological buffer, their interactions with two model proteins – cytochrome c and ribonuclease A – as well as with a single strand oligonucleotide (5′-CGCGCG-3′), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1–4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1–5 are compared to those of established ruthenium drug candidates in clinical development.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine:
           Synthesis, X-ray structure and biological activity evaluation
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Sabina Grabner, Barbara Modec, Nataša Bukovec, Peter Bukovec, Maja Čemažar, Simona Kranjc, Gregor Serša, Janez Sčančar
      To assess the potential cytostatic properties of Pt(II) complexes with 3-hydroxymethylpyridine (3-hmpy) as the only carrier ligand, novel cis-[PtCl2(3-hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2) have been prepared. Elemental analysis, FTIR spectroscopy, multinuclear NMR spectroscopy and X-ray crystallography were used to determine their structures. Based on the results obtained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and clonogenic assay on T24 human bladder carcinoma cells (T24), the most potent compound 2 was further tested for cytotoxicity in human ovarian carcinoma cell lines - cisplatin sensitive (IGROV 1) and its resistant subclone (IGROV 1/RDDP). The cytotoxicity of compound 2 in IGROV 1/RDDP is comparable to cisplatin. Furthermore, compound 2 induced severe conformational changes in plasmid DNA, which resulted in a delayed onset of apoptosis in T24 cells, and higher amounts of Pt in tumours and serum compared to cisplatin. In addition, in vivo antitumour effectiveness was comparable to that of cisplatin with a smaller reduction of animals' body weight, thus demonstrating that it is a promising transplatin analogue which deserves further studies.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Effects of Cu(II) and cisplatin on the stability of Specific protein 1
           (Sp1)-DNA binding: Insights into the regulation of copper homeostasis and
           platinum drug transport
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Dong Yan, Isamu Aiba, Helen H.W. Chen, Macus Tien Kuo
      The human high-affinity copper transporter 1 (hCtr1) transports both Cu(I) and cisplatin (cDDP). Because Cu deficiency is lethal yet Cu overload is poisonous, hCtr1 expression is transcriptionally upregulated in response to Cu deficiency but is downregulated under Cu replete conditions in controlling Cu homeostasis. The up- and down-regulation of hCtr1 is regulated by Specific protein 1 (Sp1), which itself is also correspondingly regulated under these Cu conditions. hCtr1 expression is also upregulated by cDDP via upregulation of Sp1. The underlying mechanisms of these regulations are unknown. Using gel-electrophoretic mobility shift assays, we demonstrated here that Sp1-DNA binding affinity is reduced under Cu replete conditions but increased under reduced Cu conditions. Similarly, Sp1-DNA binding affinity is increased by cDDP treatment. This in vitro system demonstrated, for the first time, that regulation of Sp1/hCtr1 expression by these agents is modulated by the stability of Sp1-DNA binding, the first step in the Sp1-mediated transcriptional regulation process.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Synthesis, structural characterization, cytotoxic properties and DNA
           binding of a dinuclear copper(II) complex
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): B.J.M. Leite Ferreira, P. Brandão, M. Meireles, Fátima Martel, Ana Correia-Branco, Diana M. Fernandes, T.M. Santos, V. Félix
      In this study a novel dinuclear copper(II) complex with adenine and phenanthroline has been synthesized and its structure determined by single crystal X-ray diffraction. In the dinuclear complex [Cu₂(μ-adenine)₂(phen)₂(H2O)2](NO3)4·0.5H2O (phen=1,10-phenanthroline) (1) the two Cu(II) centres exhibit a distorted square pyramidal coordination geometry linked by two nitrogen donors from adenine bridges leading to a Cu–Cu distance of 3.242(3)Å. Intramolecular and intermolecular π⋯π interactions as well as an H-bonding network were observed. The antitumor capacity of the complex has been tested in vitro against human cancer cell lines, cervical carcinoma (HeLa) and colorectal adenocarcinoma (Caco-2), by metabolic tests, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide as reagent. The complex 1 has remarkable low IC50 values of 0.87±0.06μM (HeLa) and 0.44±0.06μM (Caco-2), when compared with values for cisplatin against the same cell lines. The interaction of complex 1 with calf thymus DNA (CT DNA) was further investigated by absorption and fluorescence spectroscopic methods. A binding constant of 5.09×105 M−1 was obtained from UV–vis absorption studies.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Contents
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161




      PubDate: 2016-06-17T18:00:43Z
       
  • The neglected role of copper ions in wound healing
    • Abstract: Publication date: August 2016
      Source:Journal of Inorganic Biochemistry, Volume 161
      Author(s): Allison Paige Kornblatt, Vincenzo Giuseppe Nicoletti, Alessio Travaglia
      Wound healing is a complex biological process that aims to repair damaged tissue. Even though many biological and biochemical mechanisms associated with the steps of physiological wound healing are known, there is still significant morbidity and mortality due to dysregulation of physiological mechanisms. It might be useful to revise the activity of old players and their links with new, often neglected, molecular entities. This review revises new findings supporting the hypothesis that copper ions regulate the activity and/or the expression of proteins crucially involved in the wound repair process. A better understanding of these interactions might suggest potential new targets for therapeutic intervention on scars or non-healing wounds.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Bioinspired superoxide-dismutase mimics: The effects of functionalization
           with cationic polyarginine peptides
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): H.Y. Vincent Ching, Isabell Kenkel, Nicolas Delsuc, Emilie Mathieu, Ivana Ivanović-Burmazović, Clotilde Policar
      Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL] + (where HL = N-(2-hydroxybenzyl)-N,N′-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL′-Arg (n − 1) ] n + (where n =2, 4, 7 and 10) and [MnL′-Gly 1 ] + . [MnL′-Arg (n − 1) ] n + contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (K assoc) between 1.6 and 3.3×106 M−1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30V vs SCE, slightly higher than [MnL] + under the same conditions, but remain at a value that facilitates O2 − dismutation. The catalytic rate constant (k cat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL] + (k cat =5.0±0.1×106 M−1 s−1) led to a lower value (i.e. for [MnL′Gly] + , k cat =4.2±0.1×106 M−1 s−1). However, under the same conditions, k cat values between 5.0±0.4×106 M−1 s−1 and 6.6±0.1×106 M−1 s−1 were determined for [MnL′-Arg (n − 1) ] n + conjugates, indicating that the cationic residue(s) compensated for the loss in activity. Analysis of the effect of ionic strength on the k cat strongly suggested that not all the charges were involved, but only the closest ones electrostatically influenced the SOD active metal centre.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Cytotoxicity studies of water soluble coordination compounds with a
           [Mo2O2S2]2+ core
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Johanna M. Gretarsdóttir, Sandra Bobersky, Nils Metzler-Nolte, Sigridur G. Suman
      Selected molybdenum sulfur compounds with the formulas (M)[Mo2O2S4L] where (Et4N)2(1), L=S4 2−, (Et4N)(2), L=Cp, (3), L=DMF, K(5), L=serine, M=Et4N+, K+, Na+ and [Mo2O2S2L2] where Na2(4), L=cysteine, and (6), L=threonine, were prepared and subjected to cytotoxicity studies in vitro. The results were analyzed to rank the compounds according to their relative cytotoxicity and to correlate the observed toxicity to specific composition. The results guide future efforts to synthesize highly water soluble, non-toxic, compounds. Strong correlation was observed between toxicity and cation selection, as well as selection of biocompatible ligands combined with alkali metal salts. The most toxic compound analyzed showed about 50 times less cytotoxicity than the cisplatin reference compound in HT-29 cells. Preliminary results from in vivo data agree with the ranking obtained in vitro.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Synthesis, characterization and biological evaluation of novel
           Ru(II)–arene complexes containing intercalating ligands
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Stefan Nikolić, Loganathan Rangasamy, Nevenka Gligorijević, Sandra Aranđelović, Siniša Radulović, Gilles Gasser, Sanja Grgurić-Šipka
      Three new ruthenium(II)–arene complexes, namely [(η6-p-cymene)Ru(Me2dppz)Cl]PF6 (1), [(η6-benzene)Ru(Me2dppz)Cl]PF6 (2) and [(η6-p-cymene)Ru(aip)Cl]PF6 (3) (Me2dppz=11,12-dimethyldipyrido[3,2-a:2′,3′-c]phenazine; aip=2-(9-anthryl)-1H-imidazo[4,5-f] [1,10] phenanthroline) have been synthesized and characterized using different spectroscopic techniques including elemental analysis. The complexes were found to be well soluble and stable in DMSO. The biological activity of the three complexes was tested in three different human cancer cell lines (A549, MDA-MB-231 and HeLa) and in one human non-cancerous cell line (MRC-5). Complexes 1 and 3, carrying η 6-p-cymene as the arene ligand, were shown to be toxic in all cell lines in the low micromolar/subnanomolar range, with complex 1 being the most cytotoxic complex of the series. Flow cytometry analysis revealed that complex 1 caused concentration- and time-dependent arrest of the cell cycle in G2-M and S phases in HeLa cells. This event is followed by the accumulation of the sub-G1 DNA content after 48h, in levels higher than cisplatin and in the absence of phosphatidylserine externalization. Fluorescent microscopy and acridine orange/ethidium bromide staining revealed that complex 1 induced both apoptotic and necrotic cell morphology characteristics. Drug-accumulation and DNA-binding studies performed by inductively coupled plasma mass spectrometry in HeLa cells showed that the total ruthenium uptake increased in a time- and concentration-dependent manner, and that complex 1 accumulated more efficiently than cisplatin at equimolar concentrations. The introduction of a Me2dppz ligand into the ruthenium(II)-p-cymene scaffold was found to allow the discovery of a strongly cytotoxic complex with significantly higher cellular uptake and DNA-binding properties than cisplatin.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Photo-induced DNA cleavage and cytotoxicity of a ruthenium(II) arene
           anticancer complex
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Viktor Brabec, Jitka Pracharova, Jana Stepankova, Peter J. Sadler, Jana Kasparkova
      We report DNA cleavage by ruthenium(II) arene anticancer complex [(η 6-p-terp)RuII(en)Cl]+ (p-terp=para-terphenyl, en=1,2-diaminoethane, complex 1) after its photoactivation by UVA and visible light, and the toxic effects of photoactivated 1 in cancer cells. It was shown in our previous work (T. Bugarcic et al., J. Med. Chem. 51 (2008) 5310–5319) that this complex exhibits promising toxic effects in several human tumor cell lines and concomitantly its DNA binding mode involves combined intercalative and monofunctional (coordination) binding modes. We demonstrate in the present work that when photoactivated by UVA or visible light, 1 efficiently photocleaves DNA, also in hypoxic media. Studies of the mechanism underlying DNA cleavage by photoactivated 1 reveal that the photocleavage reaction does not involve generation of reactive oxygen species (ROS), although contribution of singlet oxygen (1O2) to the DNA photocleavage process cannot be entirely excluded. Notably, the mechanism of DNA photocleavage by 1 appears to involve a direct modification of mainly those guanine residues to which 1 is coordinatively bound. As some tumors are oxygen-deficient and cytotoxic effects of photoactivated ruthenium compounds containing {Ru(η6-arene)}2+ do not require the presence of oxygen, this class of ruthenium complexes may be considered potential candidate agents for improved photodynamic anticancer chemotherapy.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Alkynyl gold(I) phosphane complexes: Evaluation of
           structure–activity-relationships for the phosphane ligands, effects
           on key signaling proteins and preliminary in-vivo studies with a
           nanoformulated complex
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Vincent Andermark, Katrin Göke, Malte Kokoschka, Mohamed A. Abu el Maaty, Ching Tung Lum, Taotao Zou, Raymond Wai-Yin Sun, Elisabet Aguiló, Luciano Oehninger, Laura Rodríguez, Heike Bunjes, Stefan Wölfl, Chi-Ming Che, Ingo Ott
      Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure–activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Cobalt(II) complexes with non-steroidal anti-inflammatory drugs and
           α-diimines
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Sofia Tsiliou, Lida-Aikaterini Kefala, Antonios G. Hatzidimitriou, Dimitris P. Kessissoglou, Franc Perdih, Athanasios N. Papadopoulos, Iztok Turel, George Psomas
      Cobalt(II) complexes with a series of non-steroidal anti-inflammatory drugs (diflunisal, flufenamic acid, mefenamic acid and niflumic acid) in the presence of nitrogen-(2,2′-bipyridylamine, 2,2′-bipyridine, 1,10-phenanthroline) and/or oxygen-donor ligands (methanol) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated NSAID ligands are coordinated to Co(II) ion through their carboxylato groups in diverse binding modes. The crystal structures of complexes [Co(diflunisal-O)2(methanol)4], [Co(niflumato-O)2(methanol)4], [Co(flufenamato-O,O′)2(2,2′-bipyridylamine)], [Co(mefenamato-O,O′)2(2,2′-bipyridylamine)] and [Co3(flufenamato-O,O′)4(flufenamato-O,O,O′)2(2,2′-bipyridine)2] have been determined by X-ray crystallography. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the albumin-binding constants were determined. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the complexes were more active than the corresponding free drugs. Spectroscopic (UV and fluorescence), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode of the complexes to calf-thymus (CT) DNA and to calculate the corresponding binding constants; for all complexes, intercalation was suggested as the most possible DNA-binding mode.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • New antibacterial, non-genotoxic materials, derived from the
           functionalization of the anti-thyroid drug methimazole with silver ions
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): I. Sainis, C.N. Banti, A.M. Owczarzak, L. Kyros, N. Kourkoumelis, M. Kubicki, S.K. Hadjikakou
      The new silver(I) compound {[AgBr(μ2-S-MMI)(TPP))]2} (1) and the known one [AgCl(TPP)2(MMI)] (2) were obtained by refluxing toluene solutions of silver(I) halide with triphenylphosphine (TPP) and the anti-thyroid drug 2-mercapto-1-methyl-imidazole or methimazole (MMI). The complexes were characterized by m.p., vibrational spectroscopy (mid-FT-IR), 1H, 31P-NMR, UV–Vis spectroscopic techniques and X-ray crystallography. The antibacterial effect of 1 and 2 against the bacterial species Pseudomonas aeruginosa (PAO) and Escherichia coli was evaluated. Compound 1 exhibits comparable activity to the corresponding one of the silver nitrate which is an antibacterial drug in use. The in vivo genotoxicity of 1–2 by the mean of Allium cepa test shows no alterations in the mitotic index values due to the absence of chromosomal aberrations. The mechanism of action of the title compounds is evaluated. The DNA binding tests indicate the ability of the complexes 1–2 to modify the activity of the bacteria. The binding constants of 1–2 towards CT-DNA indicate interaction through opening of the hydrogen bonds of DNA. Docking studies on DNA-complexes interactions confirm the binding of both complexes 1–2 in the major groove of the CT-DNA. In conclusion the silver complex 1 is an anti-bacterial and non-genotoxic material, which can be applied to antibacterial drug in the future.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • [(η6-p-cymene)Ru(H2O)3]2+ binding capability of aminohydroxamates
           — A solution and solid state study
    • Abstract: Publication date: July 2016
      Source:Journal of Inorganic Biochemistry, Volume 160
      Author(s): Péter László Parajdi-Losonczi, Attila Csaba Bényei, Éva Kováts, István Timári, Tereza Radosova Muchova, Vojtech Novohradsky, Jana Kasparkova, Péter Buglyó
      Complex forming capabilities of [(η6-p-cymene)Ru(H2O)3]2+ with aminohydroxamates (2-amino-N-hydroxyacetamide (α-alahaH), 3-amino-N-hydroxypropanamide (β-alahaH) and 4-amino-N-hydroxybutanamide (γ-abhaH)) having the primary amino group in different chelatable position to the hydroxamic function were studied by pH-potentiometry, NMR and MS methods. Formation of stable [O,O] and mixed [O,O][N,N] chelated mono- and dinuclear species is detected in partially slow with α-alahaH and β-alahaH or in fast processes with γ-abhaH and the formation constants of the complexes present in aqueous solution are reported. Synthesis, spectral (NMR, IR) and ESI mass spectrometric characterization of novel dinuclear α-alaninehydroximato complexes containing the half-sandwich type Ru(II) core is described. The crystal and molecular structure of [{(η6-p-cymene)Ru}2(μ2-α-alahaH−1)(H2O)Br]Br∙H2O (1) and [{(η6-p-cymene)Ru}2(μ2-α-alahaH−1)(H2O)Cl]BF4 ∙H2O (2) was determined by single crystal X-ray diffraction method. In the complexes one half-sandwich core is coordinated by a hydroxamate [O,O] chelate while the other one by [Namino,Nhydroxamate] fashion of the bridging ligand. In both cases the remaining coordination sites of one of the Ru cores are taken by a halide ion whiles the other one by a water molecule. Reaction of 2 with 9-methylguanine indicates the N7 coordination of this simple DNA model. Complexes 1 and 2 were tested for their in vitro cytotoxicity using human-derived cancer cell lines (A2780, MCF-7, SKOV-3, HCT-116, HeLa) and showed no anti-proliferative activity in the micromolar concentration range.
      Graphical abstract image

      PubDate: 2016-06-17T18:00:43Z
       
  • Characterization and biological properties of copper(II)-ketoprofen
           complexes
    • Abstract: Publication date: Available online 4 June 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Spyros Perontsis, Antonios G. Hatzidimitriou, Olga-Aggeliki Begou, Athanasios N. Papadopoulos, George Psomas
      From the reaction of Cu(II) with non-steroidal anti-inflammatory drug ketoprofen (Hketo), complex [Cu2(keto)4(H2O)2] was isolated, while the presence of a N,N′-donor heterocyclic ligand 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or 2,2′-bipyridine (bipy) led to the formation of complexes of the formula [Cu(keto)2(N,N′-donor)(H2O)]. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structure of [Cu(keto)2(bipyam)(H2O)] was determined by X-ray crystallography. The ability of ketoprofen and its complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was evaluated; the complexes were more active compounds than free Hketo. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the binding constant of the compounds to the albumins were calculated. Diverse techniques including UV spectroscopy, cyclic voltammetry and viscosity measurements as well as fluorescence emission spectroscopy for the competitive studies of the compounds with ethidium bromide, were employed in our attempt to examine the interaction of the compounds with calf-thymus DNA; as a conclusion, intercalation is the most possible mode of binding.
      Graphical abstract image

      PubDate: 2016-06-08T09:57:56Z
       
  • Nickel-diflunisal complexes: synthesis, characterization, in vitro
           antioxidant activity and interaction with DNA and albumins
    • Abstract: Publication date: Available online 4 June 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Spyros Perontsis, Antonios G. Hatzidimitriou, Athanasios N. Papadopoulos, George Psomas
      The reaction of NiCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl) resulted in the formation of complex [Ni(difl-O)2(MeOH)4], 1. The co-existence of a N,N′-donor heterocyclic ligand 2,2′-dipyridylketone oxime (Hpko), 1,10-phenanthroline (phen), 2,2′-bipyridine (bipy) and 2,2′-bipyridylamine (bipyam) led to the formation of complexes [Ni(difl-O)2(Hpko-N,N′)2], 2, [Ni(difl)2(phen)(MeOH)2], 3, [Ni(difl)2(bipy)(MeOH)2], 4 and [Ni(difl-O,O′)2(bipyam)], 5, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 1 and 2 were determined by X-ray crystallography. The ability of the complexes to scavenge in vitro 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated; the complexes were more active scavengers than free Hdifl. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the binding constant of the compounds to the albumins were calculated. UV spectroscopy, cyclic voltammetry and viscosity measurements as well as fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed so as to monitor the interaction of the compounds with calf-thymus DNA and revealed intercalation as the most possible mode of binding.
      Graphical abstract image

      PubDate: 2016-06-08T09:57:56Z
       
  • Vanadium(IV)-chlorodipicolinate inhibits 3T3-L1 preadipocyte adipogenesis
           by activating LKB1/AMPK signaling pathway
    • Abstract: Publication date: Available online 5 June 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Liang Zhang, Ying Huang, Fang Liu, Fang Zhang, Wenjun Ding
      Our previous studies demonstrated that vanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl) alleviates lipid abnormalities in streptozotocin (STZ)-induced diabetic rats. However, the molecular mechanisms are not fully understood. In the present study, the effect of VOdipic-Cl on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes were investigated. The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of VOdipic-Cl for 8days. The cells were determined for proliferation, differentiation, lipid accumulation as well as the protein expressions of molecular targets that are involved in fatty acid synthesis. The results demonstrated that VOdipic-Cl at concentrations ranging from 2.5μM to 10μM reduced the intracellular lipid content by 10%, 22% and 30% compared to control. VOdipic-Cl down-regulated the expression of peroxisome proliferator-activated receptor (PPARγ), CCAAT element binding protein a (C/EBPα), sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4) and activated the phosphorylation of acetyl coenzyme A carboxylase (ACC), adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B1 (LKB1) in a dose-dependent manner. Further studies showed that AMPK small interfering RNA (siRNA) markedly up-regulated PPARγ, C/EBPα, FAS and FABP4 expression in the presence of VOdipic-Cl, respectively. When LKB1 was silenced with siRNA, the effect of VOdipic-Cl on AMPK phosphorylation was diminished. Taken together, these results suggested that VOdipic-Cl can inhibit 3T3-L1 preadipocyte differentiation and adipogenesis through activating the LKB1/AMPK-dependent signaling pathway. These findings raise the possibility that VOdipic-Cl may be a promising therapy in treatment of obesity.
      Graphical abstract image

      PubDate: 2016-06-08T09:57:56Z
       
  • A comparative study on the interactions of human copper chaperone Cox17
           with anticancer organoruthenium(II) complexes and cisplatin by mass
           spectrometry
    • Abstract: Publication date: Available online 15 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Lijie Li, Wei Guo, Kui Wu, Xuelei Wu, Linhong Zhao, Yao Zhao, Qun Luo, Yuanyuan Wang, Yangzhong Liu, Qingwu Zhang, Fuyi Wang
      Herein we report investigation of the interactions between anticancer organoruthenium complexes, [(η6-arene)Ru(en)(Cl)]PF6 (en=ethylenediamine, arene= p-cymene (1) or biphenyl (2)), and the human copper chaperone protein Cox17 by mass spectrometry with cisplatin as a reference. The electrospray ionization mass spectrometry (ESI-MS) results indicate much weaker binding of the ruthenium complexes than that of cisplatin to apo-Cox172s-s, the functional state of Cox17. Up to tetra-platinated Cox17 adducts were identified while only mono-ruthenated and a little amount of di-ruthenated Cox17 adducts were detected even for the reactions with 10-fold excess of the Ru complexes. However, ESI-MS analysis coupled with liquid chromatography of tryptic digests of metalated proteins identified only three platination sites as Met4, Cys27 and His47 residues, possibly due to the lower abundance or facile dissociation of Pt bindings at other sites. Complexes 1 and 2 were found to bind to the same three residues with Met4 as the major site. Inductively coupled plasma mass spectrometry results revealed that ~7mol Pt binding to 1mol apo-Cox172s-s molecules, compared to only 0.17 (1) and 0.10 (2) mol Ru to 1mol apo-Cox172s-s. This is in line with the circular dichroism results that much larger unfolding extent of α-helix of apo-Cox172s-s was observed upon cisplatin binding than that upon organoruthenium bindings. These results collectively indicate that Cox17 might not participate in the action of these anticancer organoruthenium complexes, and further verify the distinct anticancer mechanism of the organoruthenium(II) complexes from cisplatin.
      Graphical abstract image

      PubDate: 2016-05-19T05:11:26Z
       
  • G-quadruplex vs. duplex-DNA binding of nickel(II) and zinc(II) Schiff base
           complexes
    • Abstract: Publication date: Available online 14 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Riccardo Bonsignore, Alessio Terenzi, Angelo Spinello, Annamaria Martorana, Antonino Lauria, Anna Maria Almerico, Bernhard K. Keppler, Giampaolo Barone
      Novel nickel(II) (1) and zinc(II) (2) complexes of a Salen-like ligand, carrying a pyrimidine ring on the N,N′ bridge, were synthesized and characterized. Their interaction with duplex and G-quadruplex DNA was investigated in aqueous solution through UV–visible absorption, circular dichroism and viscometry measurements. The results obtained point out that, while the zinc(II) complex does not interact with both duplex and G-quadruplex DNA, the nickel(II) complex 1 binds preferentially to G-quadruplex respect to duplex-DNA, with values of the DNA-binding constants, K b , 2.6✕105 M−1 and 3.5✕104 M−1, respectively. Molecular dynamics simulations provided an atomic level model of the top-stacking binding occurring between 1 and hTelo G-quadruplex.
      Graphical abstract image

      PubDate: 2016-05-19T05:11:26Z
       
  • High kinetic stability of ZnII coordinated by the tris(histidine) unit of
           carbonic anhydrase towards solvolytic dissociation studied by affinity
           capillary electrophoresis
    • Abstract: Publication date: Available online 17 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Yosuke Sato, Hitoshi Hoshino, Nobuhiko Iki
      Solvolytic dissociation rate constants (k d) of bovine carbonic anhydrase II (CA) and its metallovariants (M-CAs, M=CoII, NiII, CuII, ZnII, and CdII) were estimated by a ligand substitution reaction, which was monitored by affinity capillary electrophoresis to selectively detect the undissociated CAs in the reaction mixture. Using EDTA as the competing ligand for Zn-CA, the dissociation followed the unimolecular nucleophilic substitution (SN1) mechanism with k d =1.0×10−7 s−1 (pH7.4, 25°C). The corresponding solvolysis half-life (t 1/2) was 80days, showing the exceptionally high kinetic stability of t Zn-CA, in contrast to the highly labile [ZnII(H2O)6]2+, where the water exchange rate (k ex) is high. This behavior is attributed to the tetrahedral coordination geometry supported by the tris(histidine) unit (His3) of CA. In the case of Co-CA, it showed a somewhat larger k d value (5.7×10−7 s−1, pH7.4, 25°C) even though it shares the same tetrahedral coordination environment with Zn-CA, suggesting that the d 7 electronic configuration of CoII in the transition state of the dissociation is stabilized by the ligand field. Among M-CAs, only Ni-CA showed a bimolecular nucleophilic substitution (SN2) reaction path in its reaction with EDTA, implying that the large coordination number (6) of NiII in Ni-CA allows EDTA to form an EDTA-Ni-CA intermediate. Overall, k d values roughly correlated with k ex values among M-CAs, with the k d value of Zn-CA deviating strongly from the trend and highlighting the exceptionally high kinetic stabilization of Zn-CA by the His3 unit.
      Graphical abstract image

      PubDate: 2016-05-19T05:11:26Z
       
  • Revised stability constant, spectroscopic properties and binding mode of
           Zn(II) to FluoZin-3, the most common zinc probe in life sciences
    • Abstract: Publication date: Available online 13 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): I. Marszałek, A. Krężel, W. Goch, I. Zhukov, I. Paczkowska, W. Bal
      2-[2-[2-[2-[bis(carboxylatomethyl)amino]-5-methoxyphenoxy]ethoxy]-4-(2,7-difluoro-3-oxido-6-oxo-4a,9a-dihydroxanthen-9-yl)anilino]acetate (FluoZin-3) is used very broadly in life sciences as intra- and extracellular Zn(II) sensor selective for Zn(II) over Co(II), Ca(II) and Mg(II) ions at their physiological concentrations. It has been used for determination of relative and absolute levels of exchangeable Zn(II) in cells and extracellular fluids. Despite its popularity, the knowledge of its acid/base and Zn(II) coordination abilities and of its spectroscopic properties remained very limited. Also the published conditional dissociation constant (C K d) values at pH7.4 are slightly discrepant, (15nM or 8.9nM). In this work we determined the C K d for Zn(II) complexation by FluoZin-3 at pH7.4 with nitrilotriacetic acid (NTA) as competitor using two independent methods: fluorimetry and UV–Vis spectroscopy. For the first time, we investigated FluoZin-3 alone and complexed with Zn(II) in the wide range of pH, determining the total of eight pK a values from fluorescence spectra and from various regions of UV–Vis spectra. The validated values of C K d (9.1±0.4nM; −log C K d =8.04) and of the absolute (pH-independent) stability constant log βZnL (8.16±0.05) were provided by fluorescence spectroscopy experiments performed at 1μM concentrations. Our experiments demonstrated that both of aminocarboxylate moieties of FluoZin-3 bind the Zn(II) ion synergistically.
      Graphical abstract image

      PubDate: 2016-05-14T04:43:16Z
       
  • The (unusual) aspartic acid in the metal coordination sphere of the
           prokaryotic zinc finger domain
    • Abstract: Publication date: Available online 11 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Gianluca D'Abrosca, Luigi Russo, Maddalena Palmieri, Ilaria Baglivo, Fortuna Netti, Ivan de Paola, Laura Zaccaro, Biancamaria Farina, Rosa Iacovino, Paolo Vincenzo Pedone, Carla Isernia, Roberto Fattorusso, Gaetano Malgieri
      The possibility of choices of protein ligands and coordination geometries leads to diverse Zn(II) binding sites in zinc-proteins, allowing a range of important biological roles. The prokaryotic Cys2His2 zinc finger domain (originally found in the Ros protein from A. tumefaciens) tetrahedrally coordinates zinc through two cysteine and two histidine residues and it does not adopt a correct fold in the absence of the metal ion. Ros is the first structurally characterized member of a family of bacterial proteins that presents several amino acid changes in the positions occupied in Ros by the zinc coordinating residues. In particular, the second position is very often occupied by an aspartic acid although the coordination of structural zinc by an aspartate in eukaryotic zinc fingers is very unusual. Here, by appropriately mutating the protein Ros, we characterize the aspartate role within the coordination sphere of this family of proteins demonstrating how the presence of this residue only slightly perturbs the functional structure of the prokaryotic zinc finger domain while it greatly influences its thermodynamic properties.
      Graphical abstract image

      PubDate: 2016-05-14T04:43:16Z
       
  • Targeting copper(II)-induced oxidative stress and the acetylcholinesterase
           system in Alzheimer's disease using multifunctional tacrine-coumarin
           hybrid molecules
    • Abstract: Publication date: Available online 5 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Slavka Hamulakova, Patrik Poprac, Klaudia Jomova, Vlasta Brezova, Peter Lauro, Lenka Drostinova, Daniel Jun, Vendula Sepsova, Martina Hrabinova, Ondrej Soukup, Pavol Kristian, Zuzana Gazova, Zuzana Bednarikova, Kamil Kuca, Marian Valko
      Alzheimer's disease is a multifactorial disease that is characterized mainly by Amyloid-β (A-β) deposits, cholinergic deficit and extensive metal (copper, iron)-induced oxidative stress. In this work we present details of the synthesis, antioxidant and copper-chelating properties, DNA protection study, cholinergic activity and amyloid-antiaggregation properties of new multifunctional tacrine-7-hydroxycoumarin hybrids. The mode of interaction between copper(II) and hybrids and interestingly, the reduction of Cu(II) to Cu(I) species (for complexes Cu-5e-g) were confirmed by EPR measurements. EPR spin trapping on the model Fenton reaction, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, demonstrated a significantly suppressed formation of hydroxyl radicals for the Cu-5e complex in comparison with free copper(II). This suggests that compound 5e upon coordination to free copper ion prevents the Cu(II)-catalyzed decomposition of hydrogen peroxide, which in turn may alleviate oxidative stress-induced damage. DNA damage protection activity of hybrids 5c and 5e in a Fenton system (copper catalyzed) was found to be in excellent agreement with the EPR spin trapping study. Compound 5g was the most effective in the inhibition of acetylcholinesterase (hAChE, IC 50 =38nM) and compound 5b was the most potent inhibitor of butyrylcholinesterase (hBuChE, IC 50 =63nM). Compound 5c was the strongest inhibitor of A-β1–40 aggregation, although a significant inhibition (>50%) was detected for compounds 5b, 5d, 5e and 5g. Collectively, these results suggest that the design and investigation of multifunctional agents containing along with the acetylcholinesterase inhibitory segment also an antioxidant moiety capable of alleviating metal (copper)-induced oxidative stress, may be of importance in the treatment of Alzheimer's disease.
      Graphical abstract image

      PubDate: 2016-05-09T06:06:59Z
       
  • Synthesis, characterization and antitumoral activity of new
           cobalt(II)complexes: effect of the ligand isomerism on the biological
           activity of the complexes
    • Abstract: Publication date: Available online 8 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Samila R. Morcelli, Érika Stilobezzia bulla, Wagner S. Terra, Rafaela O. Moreira, Franz V. Borges, Milton M. Kanashiro, Adailton J. Bortoluzzi, Leide L.F. Maciel, João Carlos de A. Almeida, Adolfo Horn Júnior, Christiane Fernandes
      The synthesis, physico-chemical characterization and cytotoxicity against five human tumoral cell lines (THP-1, U937, Molt-4, Colo205 and H460) of three new cobalt(II) coordination compounds are reported (i.e. Co(HL1)Cl (1), Co(HL2)Cl (2) and [Co(HL3)Cl]0.0.5 (CH3)2CHOH (3)). H2L2 (2-{[[2-hydroxy-3-(1-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) and H2L3 (2-{[[2-hydroxy-3-(2-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) present α and β-naphthyl groups respectively, which is absent in H2L1 (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine.These compounds were characterized by a range of physico-chemical methods. X-ray diffraction studies were performed for complex (3), indicating the formation of a mononuclear complex. Complexes (2) and (3), which contain α and β-naphthyl groups respectively, have presented lower IC50 values than those exhibited by complex (1). Complex (3) presents IC50 values lower than cisplatin against Colo205 (90 and 196 μmol L−1, respectively) and H460 (147 and 197 μmol L−1, respectively). These human neoplastic cells under investigation were also more susceptible toward complex (3) than peripheral blood mononuclear cells. Transmission electron microscopy investigations are in agreement with the loss of mitochondrial membrane potential (ΔΨm) observed by JC-1 mitochondrial potential sensor and indicate that the activity of complex (3) against leukemic cell line (U937) is mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway).
      Graphical abstract image

      PubDate: 2016-05-09T06:06:59Z
       
  • Metals content of Glossoscolex paulistus extracellular hemoglobin: Its
           peroxidase activity and the importance of these ions in the protein
           stability
    • Abstract: Publication date: Available online 5 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Celia S. Caruso, Ezer Biazin, Francisco A.O. Carvalho, Marcel Tabak, José F.R. Bachega
      In this work we investigate the presence of divalent cations bound to the Glossoscolex paulistus (HbGp) hemoglobin and their effect over the protein stability and the peroxidase (POD) activity. Atomic absorption studies show that the HbGp iron content is consistent with the presence of 144 ions per protein. Moreover, using iron as a reference, the content of calcium was estimated as 30±4 ions per protein, independently of the EDTA pre-treatment or not prior to the acidic treatment performed in the protein digestion. The zinc content was 14±2 ions in the absence of EDTA pre-treatment, and 3±1 ions per protein in the presence of EDTA pre-treatment, implying the presence of one zinc ion per protomer (1/12 of the whole molecule). Finally, the copper concentration is negligible. Different from the vertebrate hemoglobins, where the effectors are usually organic anions, the hexagonal bilayer hemoglobins have as effectors inorganic cations that increase the oxygen affinity and stabilize the structure. Previous studies have suggested that the presence of divalent cations, such as copper and zinc, is related to the different types of antioxidant enzymatic activities as the superoxide dismutase (SOD) activity shown by giant hemoglobin from Lumbricus terrestris (HbLt). Recently, studies on HbGp crystal structure have confirmed the presence of Zn2+ and Ca2+ binding sites. The Ca2+ sites are similar as observed in the HbLt crystal structure. Otherwise, the Zn2+ sites have no relation with those observed in Cu/Zn SODs. Our peroxidase assays with guaiacol confirm the POD activity and the effect of the zinc ions for HbGp. Our present results on HbGp metal content and their stability effects is the first step to understand the role of these cations in HbGp function in the future.
      Graphical abstract image

      PubDate: 2016-05-09T06:06:59Z
       
  • Surface complex of ZnTMPyP4 metalloporphyrin with double-stranded
           poly(a)-poly(U)
    • Abstract: Publication date: Available online 6 May 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): G. Tolstykh, V. Sizov, A. Kudrev
      This communication presents synthesis and spectral characterization of metalloporphyrin [Zn(X)TMPyP4] (TMPyP4 is 5,10,15,20-tetrakis (N-methylpyridinium-4-yl)porphyrin), and studies its binding onto anionic surface sites of synthetic double stranded polynucleotide Poly(A)-Poly(U). [Zn(X)TMPyP4] binding with Poly(A)-Poly(U) was monitored by UV–Vis absorbance spectroscopy, two fluorescence spectroscopies and 1H NMR in a working aqueous medium of 0.15M ionic strength, pH7.0 and at 25°C. The evidence provided by spectroscopic measurements and multivariate data analysis suggests the use of this metalloporphyrin as a probe for investigation of the polynucleotide surface. In contrast to TMPyP4 intercalation, an outside adsorption of [Zn(X)TMPyP4] induces an attenuation of luminescence intensity and has little influence on the shape of luminescence band. Special attention was paid to the quantitative description of the interaction between neighboring ligands on the Poly(A)-Poly(U) surface. The intrinsic binding constant to an isolated binding site lgKin 5.8±0.1, the cooperativity parameter ω 1.8±0.2, and number of monomers occupied by a ligand n =2 (25°C; pH7.0) were calculated based upon the recently proposed non-linear least-squares fitting procedure. The discovered cooperativity of binding of [Zn(X)TMPyP4] metalloporphyrin to Poly(A)-Poly(U) is significantly lower as compared to free porphyrin TMPyP4, reflecting minimal mutual influence between the nearest neighboring ligands bound with functional PO4 − groups of the polynucleotide surface.
      Graphical abstract image

      PubDate: 2016-05-09T06:06:59Z
       
  • Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of
           chirality on their interaction with biomolecules
    • Abstract: Publication date: Available online 8 April 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Chew Hee Ng, Cheang Wei Chan, Jing Wei Lai, Ing Hong Ooi, Kok Vei Chong, Mohd Jamil Maah, Hoi Ling Seng
      Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3 −; ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl−; ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)]+ and [Cu(phen)(d-ala)(H2O)]+, have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.
      Graphical abstract image

      PubDate: 2016-04-09T02:21:12Z
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
Home (Search)
Subjects A-Z
Publishers A-Z
Customise
APIs
Your IP address: 54.92.136.130
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2015