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  Subjects -> CHEMISTRY (Total: 767 journals)
    - ANALYTICAL CHEMISTRY (45 journals)
    - CHEMISTRY (532 journals)
    - CRYSTALLOGRAPHY (22 journals)
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    - INORGANIC CHEMISTRY (40 journals)
    - ORGANIC CHEMISTRY (40 journals)
    - PHYSICAL CHEMISTRY (64 journals)

INORGANIC CHEMISTRY (40 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 19)
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: 4)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal  
Current Methods in Inorganic Chemistry     Full-text available via subscription  
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 6)
European Polymer Journal     Hybrid Journal   (Followers: 41)
Heterocyclic Communications     Full-text available via subscription   (Followers: 2)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 5)
Inorganic Chemistry     Full-text available via subscription   (Followers: 19)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 7)
Inorganic Chemistry Frontiers     Full-text available via subscription  
Inorganic Materials     Hybrid Journal   (Followers: 2)
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: 2)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 6)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic Chemistry     Open Access  
Journal of Polymer Engineering     Full-text available via subscription   (Followers: 7)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 7)
Open Journal of Inorganic Chemistry     Open Access   (Followers: 1)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 8)
Polyoxometalate Chemistry     Open Access  
Reviews in Inorganic Chemistry     Full-text available via subscription  
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: 3)
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
   Journal TOC RSS feeds Export to Zotero [4 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0162-0134
     Published by Elsevier Homepage  [2563 journals]   [SJR: 0.807]   [H-I: 79]
  • Ferrocifen derivatives that induce senescence in cancer cells: Selected
           examples
    • Abstract: Publication date: Available online 6 September 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Céline Bruyère , Véronique Mathieu , Anne Vessières , Pascal Pigeon , Siden Top , Gérard Jaouen , Robert Kiss
      Platinum coordination complexes represent an important class of anti-tumor agents. Due to recognized drawbacks, research into other types of metallodrugs has been diversified with the aim of finding new chemical entities with alternative mechanisms of action to overcome classical chemoresistance. P5 and DP1, two closely related ferrocenyl complexes bearing a similar ferrocenyl-ene-phenyl motif and displaying marked differences in their conformations and oxidation state versatility were assayed in cancer cell models characterized by various sensitivities to pro-apoptotic stimuli. P5 and DP1 exert growth inhibitory effects between 0.5 and 10μM against glioma and melanoma cells including pluripotent stem-like cells. These effects are due, at least partly, to senescence induction with typical SA-β-galactosidase staining and senescence-associated secretory phenotype (SASP) as measured by the secretion of IL-1α, IL-1β, IL-6, IL-8 and TNF-α. Regulation of these cytokines’ secretion may be related to AP-1 and other transcription factors unrelated to senescence. An in vivo graft of B16F10 cells after in vitro pre-incubation with DP1 or P5 led to increased survival in mice. In conclusion, P5 and DP1 ferrocenyl complexes induce senescence in various cancer cell models associated with distinct sensitivity to pro-apoptotic stimuli.
      Graphical abstract image Highlights This study reports that synthetic ferrocenyl complexes can overcome apoptosis resistance by inducing irreversible senescence associated with typical secretory phenotype. However and interestingly this senescence occurs via unclassical pathway.

      PubDate: 2014-09-11T03:12:45Z
       
  • Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate
           phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: Covalent vs
           non-covalent DNA binding, DNA cleavage and cytotoxicity
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Chandrasekaran Rajarajeswari , Mani Ganeshpandian , Mallayan Palaniandavar , Anvarbatcha Riyasdeen , Mohammad Abdulkadher Akbarsha
      A series of copper(II) complexes of the types [Cu(L)(phen)](ClO4) 1–2, where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1H-benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1H-benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and [Cu(L)(phen)](ClO4)2 3–6, where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1H-benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1H-benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1H-benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1–6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a–2a and [Cu(3N)Cl2] 3a–6a. On prolonged incubation, all the complexes 1–6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a–6a, and have the potential to act as efficient cytotoxic drugs.
      Graphical abstract image

      PubDate: 2014-09-11T03:12:45Z
       
  • [Fe(CN)5(isoniazid)]3−: An iron isoniazid complex with redox
           behavior implicated in tuberculosis therapy
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Eduardo Henrique Silva Sousa , Francisca Gilmara de Mesquita Vieira , Jennifer S. Butler , Luiz Augusto Basso , Diógenes S. Santiago , Izaura C.N. Diógenes , Luiz Gonzaga de França Lopes , Peter J. Sadler
      Tuberculosis has re-emerged as a worldwide threat, which has motivated the development of new drugs. The antituberculosis complex Na3[Fe(CN)5(isoniazid)] (IQG607) in particular is of interest on account of its ability to overcome resistance. IQG607 has the potential for redox-mediated-activation, in which an acylpyridine (isonicotinoyl) radical could be generated without assistance from the mycobacterial KatG enzyme. Here, we have investigated the reactivity of IQG607 toward hydrogen peroxide and superoxide, well-known intracellular oxidizing agents that could play a key role in the redox-mediated-activation of this compound. HPLC, NMR and electronic spectroscopy studies showed a very fast oxidation rate for bound isoniazid, over 460-fold faster than free isoniazid oxidation. A series of EPR spin traps were used for detection of isonicotinoyl and derived radicals bound to iron. This is the first report for an isonicotinoyl radical bound to a metal complex, supported by 14N and 1H hyperfine splittings for the POBN and PBN trapped radicals. POBN and PBN exhibited average hyperfine coupling constants of aN =15.6, aH =2.8 and aN =15.4, aH =4.7, respectively, which are in close agreement to the isonicotinoyl radical. Radical generation is thought to play a major role in the mechanism of action of isoniazid and this work provides strong evidence for its production within IQG607, which, along with biological and chemical oxidation data, support a redox-mediated activation mechanism. More generally the concept of redox activation of metallo prodrugs could be applied more widely for the design of therapeutic agents with novel mechanisms of action.
      Graphical abstract image

      PubDate: 2014-09-06T02:30:30Z
       
  • Disruption of heme-peptide covalent cross-linking in mammalian peroxidases
           by hypochlorous acid
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Husam M. Abu-Soud , Dhiman Maitra , Faten Shaeib , Sana N Khan , Jaeman Byun , Ibrahim Abdulhamid , Zhe Yang , Ghassan M. Saed , Michael P. Diamond , Peter R. Andreana , Subramaniam Pennathur
      Myeloperoxidase (MPO), lactoperoxidase (LPO) and eosinophil peroxidase (EPO) play a central role in oxidative damage in inflammatory disorders by utilizing hydrogen peroxide and halides/pseudo halides to generate the corresponding hypohalous acid. The catalytic sites of these enzymes contain a covalently modified heme group, which is tethered to the polypeptide chain at two ester linkages via the methyl group (MPO, EPO and LPO) and one sulfonium bond via the vinyl group (MPO only). Covalent cross-linking of the catalytic site heme to the polypeptide chain in peroxidases is thought to play a protective role, since it renders the heme moiety less susceptible to the oxidants generated by these enzymes. Mass-spectrometric analysis revealed the following possible pathways by which hypochlorous acid (HOCl) disrupts the heme-protein cross-linking: (1) the methyl-ester bond is cleaved to form an alcohol; (2) the alcohol group undergoes an oxygen elimination reaction via the formation of an aldehyde intermediate or undergoes a demethylation reaction to lose the terminal CH2 group; and (3) the oxidative cleavage of the vinyl-sulfonium linkage. Once the heme moiety is released it undergoes cleavage at the carbon-methyne bridge either along the δ–β or a α–γ axis to form different pyrrole derivatives. These results indicate that covalent cross-linking is not enough to protect the enzymes from HOCl mediated heme destruction and free iron release. Thus, the interactions of mammalian peroxidases with HOCl modulates their activity and sets a stage for initiation of the Fenton reaction, further perpetuating oxidative damage at sites of inflammation.
      Graphical abstract image

      PubDate: 2014-09-06T02:30:30Z
       
  • Biological activity of a series of cisplatin-based aliphatic
           bis(carboxylato) Pt(IV) prodrugs: How long the organic chain should
           be?
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Ilaria Zanellato , Ilaria Bonarrigo , Donato Colangelo , Elisabetta Gabano , Mauro Ravera , Manuela Alessio , Domenico Osella
      The biological properties of a series of cisplatin-based Pt(IV) prodrug candidates, namely trans,cis,cis-[Pt(carboxylato)2Cl2(NH3)2], where carboxylato=CH3(CH2)nCOO− [(1), n=0; (2), n=2; (3), n=4; (4), n=6] having a large interval of lipophilicity are discussed. The stability of the complexes was tested in different pH conditions (i.e. from 1.0 to 9.0) to simulate the hypothetical conditions for an oral route of administration, showing a high stability (>90%). The transformation into their active Pt(II) metabolites was demonstrated in the presence of ascorbic acid, with a pseudo-first order kinetics, the half-time of which smoothly decreases as the chain length of carboxylic acid increases. Their antiproliferative activity has been evaluated in vitro on a large panel of human cancer cell lines. As expected, the potency increases with the chain length: 3 and 4 resulted by far more active than cisplatin on all cell lines of about one or two orders of magnitude, respectively. Both complexes retained their activity also on cisplatin-resistant cell line, and exhibited a progressive increase of the selectivity compared with non-tumor cells. These results were confirmed with more prolonged treatment (up to 14days) studied on multicellular tumor spheroids (MCTSs). In this case the Pt(IV) complexes exert a protracted antiproliferative action, even if the drug is removed from the culture medium. Finally, in a time-course experiment of the total platinum evaluation in mice blood (after a single oral administration of the title complexes), 2 gave the best results, representing a good compromise between lipophilicity and water solubility, that increase and decrease respectively on passing from 1 to 4.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Using methyl as substituted-radical in n-phen enhances the anticancer
           activities of [(DMF)Cu(n-phen)(NO3−)2]
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Bo Zhang , Xiaoming Lu , Guo Wang , Weichuan Zhang , Sifeng Xia , Yuyou Chen
      In order to seek better ligand for anticancer drug, we choose 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) as predominant ligands, and synthetize two complexes:[(DMF)Cu(phen)(NO3)2] (1) and [(DMF)Cu(2,9-dmp)(NO3)2] (2) (DMF is dimethyl formamide). As for the five kinds of cancer cells, including A-549, Bel-7402, HCT-8, MDCK and L-1210 cells, our complexes showed higher inhibition ratio compared with anticancer drug 5-Fu (fluorouracil), ligand phenanthroline and Cu(NO3)2. It's worth noting that complex 2's anticancer activity is much more efficient than that of complex 1. This is because there are di-substituted-methyl in 2,9-dmp. By calculating, we found Δcomplexes <Δphenanthroline which showed that the energy gap between π⁎ and π of the phenanthroline is decreased through coordination with CuII. Computational ΔG2 <ΔG, and bond length (CuN)1 <(CuN)2 revealed that the coordinated 2,9-dmp is easier to dissociate with CuII than phen, which is confirmed by the absorption peak at 460nm in UV–visible (UV–vis) spectra of complex 2. In summary, the phenanthroline is activated by CuII-coordination, which is beneficial for anticancer. More importantly, the substituted-methyl radicals stimulated the phenanthroline and enhanced the anticancer properties more efficiently.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Y3+, La3+, and some bivalent metals inhibited the opening of the
           Tl+-induced permeability transition pore in Ca2+-loaded rat liver
           mitochondria
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Sergey Korotkov , Svetlana Konovalova , Larisa Emelyanova , Irina Brailovskaya
      We showed earlier that diminution of 2,4-dinitrophenol (DNP)-stimulated respiration and increase of both mitochondrial swelling and electrochemical potential (ΔΨmito) dissipation in medium containing TlNO3 and KNO3 were caused by opening of Tl+-induced mitochondrial permeability transition pore (MPTP) in the inner membrane of Ca2+-loaded rat liver mitochondria. The MPTP opening was studied in the presence of bivalent metal ions (Sr2+, Ba2+, Mn2+, Co2+ and Ni2+), trivalent metal ions (Y3+ and La3+), and ruthenium red. We found that these metal ions (except Ba2+ and Co2+) as well as ruthenium red inhibited to the MPTP opening that manifested in preventing both diminution of the DNP-stimulated respiration and increase of the swelling and of the ΔΨmito dissipation in medium containing TlNO3, KNO3, and Ca2+. Inhibition of the MPTP opening by Sr2+ and Mn2+ is suggested because of their interaction with high affinity Ca2+ sites, facing the matrix side and participating in the MPTP opening. The inhibitory effects of metal ions (Y3+, La3+, and Ni2+), and ruthenium red are accordingly discussed in regard to competitive and noncompetitive inhibition of the mitochondrial Ca2+-uniporter. High concentrations (50μM) of Y3+ and La3+ favored of MPTP opening in the inner membrane of rat liver mitochondria in Ca2+ free medium containing TlNO3. The latter MPTP opening was markedly eliminated by MPTP inhibitors (cyclosporine A and ADP).
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III)
           complexes
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Voin Petrović , Sandra Petrović , Gordana Joksić , Jasmina Savić , Mirjana Čolović , Maria Agostina Cinellu , Lara Massai , Luigi Messori , Vesna Vasić
      Na+/K+-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy source to drive excess Na+ ions out of the cell in exchange for K+ ions. We explored whether three representative cytotoxic gold(III) compounds might interfere with Na+/K+-ATPase and cause its inhibition at pharmacologically relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy=2,2′-bipyridine), [Au(pydmb-H)(CH3COO)2] (pydmb-H=deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipydmb-H)(OH)][PF6] (bipydmb-H=deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na+/K+-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na+/K+-ATPase inhibition. It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Mixed ligand copper(II) complexes of 2,9-dimethyl-1,10-phenanthroline:
           Tridentate 3N primary ligands determine DNA binding and cleavage and
           cytotoxicity
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Mani Ganeshpandian , Sethu Ramakrishnan , Mallayan Palaniandavar , Eringathodi Suresh , Anvarbatcha Riyasdeen , Mohammad Abdulkadher Akbarsha
      A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(L)(2,9-dmp)](ClO4)2 1–4, where L is a tridentate 3N ligand such as diethylenetriamine (L1) (1) or N-methyl-N′-(pyrid-2-yl-methyl)ethylenediamine (L2) (2) or di(2-picolyl)amine (L3) (3) or bis(pyrid-2-ylmethyl)-N-methylamine (L4) (4) and 2,9-dmp is 2,9-dimethyl-1,10-phenanthroline, has been isolated and characterized. The complexes 1 and 3 possess square-based pyramidal coordination geometry. Absorption spectral studies reveal that the intrinsic DNA binding affinity varies as 1 > 2 > 3 > 4. The higher DNA binding affinity of 1 arises from L1, which offers lower steric hindrance toward intercalation of 2,9-dmp co-ligand into DNA base pairs and is involved in hydrogen bonding interaction with DNA. Interestingly, all the complexes cleave pUC19 supercoiled DNA in the absence of an activating agent. They also exhibit oxidative (H2O2) DNA cleavage ability, which varies as 1 > 2 > 3 > 4, the highest cleavage efficiency of 1 being due to the largest amount of ROS it generates. The tryptophan emission-quenching experiment reveals that the stronger binding of 3 and 4 with bovine serum albumin (BSA) in the hydrophobic region, which is in line with DNA viscosity measurements. The IC50 values of 1–4 for MCF-7 breast cancer cell line are lower than that of cisplatin. Flow cytometry analysis reveals that 1 mediates the arrest of S and G2/M phases in the cell cycle progression at 24h harvesting time, which progresses into apoptosis. Hoechst 33258 staining studies indicate the higher potency of 1 to induce apoptosis.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Synthesis, DNA interaction and anticancer activity of copper(II) complexes
           
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Jie-Wen Liang , Yi Wang , Ke-Jie Du , Guan-Ying Li , Rui-Lin Guan , Liang-Nian Ji , Hui Chao
      Three novel copper(II) complexes CuL1Cl2 (1) (L1 =4′-(3-methoxyphenyl)-2,2′:6′- 2″-terpyridine), CuL2Cl2 (2) (L2 =4′-(4-methoxyphenyl)-2,2′:6′-2″-terpyridine) and CuL3Cl2 (3) (L3 =4′-(3,5-dimethoxyphenyl)-2,2′:6′-2″-terpyridine) have been synthesized and characterized. Absorption spectral titration experiments, ethidium bromide displacement assays, and cyclic voltammetric experiments were carried out and the results suggested that these complexes bound to DNA through an intercalative mode. Moreover, these complexes were found to cleave pBR322 DNA efficiently in the presence of glutathione (GSH), and exhibited good anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage was also observed by acridine orange/ethidium bromide (AO/EB) staining assays and comet assays. These results demonstrated that these three Cu(II) complexes caused DNA damage and induced the apoptosis of HeLa cells. Mechanistic investigations revealed the participation of reactive oxygen species which can be trapped by reactive oxygen species (ROS) radical scavengers and ROS sensors.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • A dimerization interface mediated by functionally critical residues
           creates interfacial disulfide bonds and copper sites in CueP
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Luciano A. Abriata , Lucas B. Pontel , Alejandro J. Vila , Matteo Dal Peraro , Fernando C. Soncini
      CueP confers bacterial copper resistance in the periplasm, particularly under anaerobic conditions, through an unknown mechanism. The only available structure and limited solution data suggest that CueP forms noncovalent dimers in solution, whereas sequence conservation suggests important roles for three cysteines and two histidines as copper ligands. Here we report evidence of a dimerization equilibrium mediated by a newly identified interface of functional relevance, which occludes internal copper sites and disulfide bonds but allows for intra- and interchain disulfide bonding, an extensive disulfide relay, and interfacial copper sites. Our results suggest a role for CueP linking redox-state sensing and copper detoxification.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • New heteronuclear gold(I)–platinum(II) complexes with cytotoxic
           properties: Are two metals better than one?
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Margot Wenzel , Emilia Bigaeva , Philippe Richard , Pierre Le Gendre , Michel Picquet , Angela Casini , Ewen Bodio
      A series of mono- and heterodinuclear gold(I) and platinum(II) complexes with a new bipyridylamine-phosphine ligand have been synthesized and characterized. The X-ray structures of the ligand precursor 4-iodo-N,N-di(pyridin-2-yl)benzamide, and of one gold derivative are reported. All the complexes display antiproliferative properties in vitro in human cancer cells in the range of cisplatin or higher, which appear to correlate with compounds' uptake. Interestingly, studies of the interactions of the compounds with models of DNA indicate different mechanisms of actions with respect to cisplatin. The biological activity study of these complexes provides useful information about the interest of designing multimetallic complexes for enhanced cytotoxic properties.
      Graphical abstract image

      PubDate: 2014-09-01T01:45:57Z
       
  • Structure and biological perspectives of Cu(II)–indomethacin
           complexes
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Alketa Tarushi , Catherine P. Raptopoulou , Vassilis Psycharis , Dimitris P. Kessissoglou , Athanasios N. Papadopoulos , George Psomas
      The copper(II) complexes with the non-steroidal anti-inflammatory drug indomethacin (Hindo) in the presence of the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2′-bipyridylamine (bipyam) have been synthesized and characterized. The crystal structures of [Cu(indo)2(bipy)]∙1.5MeOH∙0.5H2O and [Cu(indo)2(phen)] ∙1.85MeOH∙0.15H2O have been determined by X-ray crystallography. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with the previously reported complex [Cu2(indo)4(H2O)2] being the most active. The complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. UV study of the interaction of the complexes with calf-thymus (CT) DNA has shown that the complexes can bind to CT DNA with [Cu(indo)2(bipyam)] showing the highest binding constant to CT DNA (Kb =1.56(±0.19)×106 M−1). The complexes can bind to CT DNA via intercalation as concluded by cyclic voltammetry, DNA viscosity measurements and competitive studies with ethidium bromide (EB) which revealed the ability of the complexes to displace the DNA-bound EB.
      Graphical abstract image

      PubDate: 2014-08-16T00:45:22Z
       
  • Behavior of the potential antitumor VIVO complexes formed by flavonoid
           ligands. 1. Coordination modes and geometry in solution and at the
           physiological pH
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Daniele Sanna , Valeria Ugone , Giuseppe Lubinu , Giovanni Micera , Eugenio Garribba
      The coordination modes and geometry assumed in solution by the potent antitumor oxidovanadium(IV) complexes formed by different flavonoids were studied by spectroscopic (Electron Paramagnetic Resonance, EPR) and computational (Density Functional Theory, DFT) methods. A series of bidentate flavonoid ligands (L) with increasing structural complexity was examined, which can involve (CO, O−) donors and formation of five- and six-membered chelate rings, or (O−, O−) donors and five-membered chelate rings. The geometry corresponding to these coordination modes can be penta-coordinated, [VOL2], or cis-octahedral, cis-[VOL2(H2O)]. The results show that, at physiological pH, ligands provided with (CO, O−) donor set yield cis-octahedral species with “maltol-like” coordination when five-membered chelate rings are formed (as with 3-hydroxyflavone), while penta-coordinated structures with “acetylacetone-like” coordination are preferred when the chelate rings are six-membered (as with chrysin). When both the binding modes are possible, as with morin, the “acetylacetone-like” coordination is observed. For the ligands containing a catecholic donor set, such as 7,8-dihydroxyflavone, baicalein, fisetin, quercetin and rutin, the formation of square pyramidal complexes with (O−, O−) “catechol-like” coordination and five-membered chelate rings is preferred at physiological pH. The determination of the different coordination modes and geometry is important to define the biotransformation in the blood and the interaction of these complexes with the biological membranes.
      Graphical abstract image

      PubDate: 2014-08-16T00:45:22Z
       
  • The antimicrobial and antibiofilm activities of copper(II) complexes
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Michael L. Beeton , Janice R. Aldrich-Wright , Albert Bolhuis
      Biofilm-related bacterial infections pose a significant problem, as they are generally more tolerant to antibiotics and the immune system. Development of novel compounds with antibiofilm activity is therefore paramount. In this study we have analysed metal complexes of the general structure [M(IL)(AL)]2+ (where IL represents functionalised 1,10-phenanthrolines and AL represents 1S,2S- or 1R,2R-diaminocyclohexane) and [Cu(IL)3]2+. Antimicrobial activity was tested on a number of bacterial strains, showing that copper(II) compounds were active against both Gram-positive and Gram-negative bacteria, albeit that activity was generally higher for the former. The antibiofilm activity was then determined against a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA). Strikingly, the copper complexes tested showed significant activity against biofilms, and were better in the removal of biofilms than vancomycin, an antibiotic that is currently used in the treatment of MRSA infections.
      Graphical abstract image

      PubDate: 2014-08-13T00:31:32Z
       
  • Spectroscopic, luminescence and in vitro biological studies of solid
           ketoprofen of heavier trivalent lanthanides and yttrium(III)
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): D.A. Gálico , M.G. Lahoud , M.R. Davolos , R.C.G. Frem , T.F.C. Fraga-Silva , J. Venturini , M.S.P. Arruda , G. Bannach
      Solid-state compounds of the general formulae [ML3] (M=Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y; L=ketoprofen) were synthesized and characterized using infrared, diffuse reflectance and luminescence spectroscopies. IR data suggested that the carboxylate group in ketoprofen is coordinated to the metals as a bidentate ligand. The triplet state energy level was determined using the Gd3+ complex, which exhibited a ketoprofen blue luminescence when excited in the UV region. The compound containing Tb3+ ion was sensitized by the ligand and emitted in the green region of the visible spectrum. On the other hand, for the analogous species containing the dysprosium ion, a competition for luminescence between the Dy3+ and the ligand levels was observed. Finally, Tm3+ complex exhibits only ligand luminescence. These optical behaviors are discussed based on rare earth energy diagrams. In addition, the compounds were evaluated for their anti-inflammatory activities. All the compounds showed a higher production of H2O2 and IL-10 than the ketoprofen, suggesting that the compounds exhibited an immunomodulatory effect and this opens up new perspectives for immunotherapeutic approaches.
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      PubDate: 2014-08-13T00:31:32Z
       
  • Effect of glucosamine conjugation to zinc(II) complexes of a bis-pyrazole
           ligand: Syntheses, characterization and anticancer activity
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Sudipta Bhattacharyya , Amrita Sarkar , Suman Kr. Dey , Arindam Mukherjee
      The bis(3,5-dimethyl-1H- pyrazol-1yl)acetic acid (bdmpza) ligand was conjugated with tert-butyl-N-(2-aminoethyl) carbonate, methyl-2-amino-4-(methylthio)butanoate and 1,3,4,6-tetra-O-acetyl-β-d-glucosamine hydrochloride via amide coupling method to form three ligands L1–L3 which were then reacted with Zn(II) salts to form four zinc complexes (1–4). The complexes were characterized by 1H NMR, 13C NMR, electrospray ionization mass spectrometry (ESI-MS), FT-IR, CHN analyses. Complexes 1, 2 and 4 were also characterized by single crystal X-ray diffraction. It was found that Zn(II) salts could selectively remove the acetyl group from anomeric position leaving everything else intact. The cytotoxicity studies of the ligand and the complexes showed that the conjugation to acetylated glucosamine enhances cytotoxic ability although the complexes become more hydrophilic. Cytotoxicity studies in human breast adenocarcinoma (MCF-7), human cervical cancer (HeLa WT) and human lung adenocarcinoma (A549) showed that the acetylated glucosamine conjugation to the bis-pyrazole ligated Zn(II) complex led to 2–4 fold increase in cytotoxicity (IC50 values ca. 57–80μM) against HeLa WT and MCF-7 cell lines. The Zn(II) complex bearing the acetylated glucosamine inhibits the cell cycle in the G2/M phase of MCF-7 cell line. ICP-MS data shows more accumulation of Zn(II) inside the cell upon use of complex 4 as compared to Zn(II) salts or the other presented complexes. Further studies suggest that the mitochondrial transmembrane potential changes in the presence of complex 4 and caspase-7 is activated by Zn(II) salts but the activation is much more by complex 4 and hence there is apoptosis and dose dependent chromatin condensation/nuclear fragmentation as observed by microscopy.
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      PubDate: 2014-08-13T00:31:32Z
       
  • Ligand effect and cooperative role of metal ions on the DNA cleavage
           efficiency of mono and binuclear Cu(II) macrocyclic ligands complexes
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Nataraj Chitrapriya , Wei Wang , Yoon Jung Jang , Seog K. Kim , Jung Hee Kim
      Two binuclear Cu(II) complexes of N-functionalized macrocycle ligands, namely 1,3-bis(1,4,7-triaza-1-cyclonomyl)propane and 1-(3-(1,4,7-triazonan-1-yl)propyl)-1,4,7,10-tetraazacyclo-dodecane, were synthesized and their ability to hydrolyze the cleavage of supercoiled plasmid DNA (pBR322) was compared with that of structurally related non-functionalized mononuclear Cu(II) complexes. The former, binuclear Cu(II) complex with the symmetrical ligand exhibited enhanced double-strand cleavage activity compared to the other three complexes at the same [Cu2+] concentration. In contrast, the latter binuclear complex with unsymmetrical macrocylic ligand did not give rise to double-strand DNA cleavage. The linear DNA formation induced by the mononuclear Cu(II) 1,4,7,10-tetraazacyclo-dodecane complex was realized via a non-random double-stranded scission process. The differential cleavage activity is discussed in relation to dimer formation, effective cooperation and coordination environment of the metal center. The hydrolytic cleavage by the copper complexes without H2O2 is supported by evidence from an anaerobic reaction, free radical quenching, and nitro blue tetrazolium assay. In contrast, both the binuclear complexes cleaved supercoiled DNA efficiently to Form III (linearized DNA) in the presence of H2O2, indicating that nuclearity is a crucial parameter in oxidative cleavage. The radical scavenger inhibition study and nitro blue tetrazolium assay suggested the involvement of H2O2 and superoxide ions in the oxidative cleavage of DNA by the binuclear complexes.
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      PubDate: 2014-08-13T00:31:32Z
       
  • Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II)
           
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Franco Bisceglie , Silvana Pinelli , Rossella Alinovi , Matteo Goldoni , Antonio Mutti , Alessandro Camerini , Lorenzo Piola , Pieralberto Tarasconi , Giorgio Pelosi
      This paper reports the synthesis and characterization of trans-cinnamaldehyde thiosemicarbazone (Htcin), cuminaldehyde thiosemicarbazone (Htcum) and their copper and nickel complexes. All the compounds, which on healthy cells (human fibroblasts) show a neglectable cytotoxicity, were screened in vitro in cell line U937 for their antileukemic activity. These compounds, in spite of their molecular similarity, present variegated behaviors. Htcin shows no inhibition activity in U935 cells, while both its metal complexes inhibit proliferation with IC50 at μM concentrations. The other ligand, Htcum, and its metal complexes, besides inhibiting proliferation, induce apoptosis. The cell cycle analysis highlights a G2/M checkpoint stop suggesting a possible direct action on DNA or on topoisomerase IIa. From CD and UV spectroscopy experiments, the DNA results to be not the main target of all these molecules, while both copper complexes are effective topoisomerase IIa inhibitors. All of these molecules activate caspase-9 and caspase-3, while caspase-8 activity is significantly induced by both cinnamaldehyde metal complexes. Tests on PgP and intracellular metal concentrations (determined by mean of atomic absorption spectrometry) show that the compounds tend to accumulate in the cytoplasm and that the cells do not manage to pump out copper and nickel ions.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Copper-binding properties of the BIR2 and BIR3 domains of the X-linked
           inhibitor of apoptosis protein
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Yiwen Liang , Patrick M. Ewing , Willem J. Laursen , Valerie T. Tripp , Shubha Singh , Kathryn E. Splan
      The X-linked inhibitor of apoptosis protein (XIAP) is a zinc metalloprotein that has recently been implicated in copper homeostasis. XIAP mediates apoptosis via the inhibition of caspase enzymes through multiple baculovirus IAP repeat (BIR) domains, wherein zinc is coordinated by three cysteine amino acids and one histidine amino acid. XIAP binds copper ions directly at one or more unspecified sites, indicating that the protein may function as a copper sensor. We report the copper-binding properties of an XIAP construct containing the BIR2 and BIR3 domains. Absorption and emission spectroscopic measurements show that XIAP exhibits only a low-to-moderate affinity for Cu(II), but a strong affinity for Cu(I). Cu(I) is observed to bind at multiple sites within the BIR2 and BIR3 domains, including the CXXC motifs of the zinc structural sites and multiple BIR2 surface sites. Mutagenesis-based experiments reveal that surface cysteine residues mediate binding in the BIR2 domain and induce protein oligomerization under elevated copper concentrations. These results constitute the first spectroscopic evidence of copper–XIAP interactions.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Cu(II) inhibits hIAPP fibrillation and promotes hIAPP-induced beta cell
           apoptosis through induction of ROS-mediated mitochondrial dysfunction
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Lijuan Ma , Xiaoling Li , Yi Wang , Wenjie Zheng , Tianfeng Chen
      Human islet amyloid polypeptide (hIAPP), the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM), plays a central role in the loss of insulin-secreting pancreatic beta cells. Misfolded hIAPP fibrillating in islet beta cells may be one of the causations for T2DM. Studies have showed that fibrosis of hIAPP was inhibited by copper compounds while hIAPP-induced cytotoxicity was greatly stimulated. In this study, the suppression effects of three different forms of copper compounds CuCl2, CuSO4 and Cu(Gly)2 on amyloid fibril formation were examined in vitro. The results demonstrated that Cu(II) could interact with hIAPP to suppress the fibrosis without involvement of the anions. The fibrosis of hIAPP was inhibited by CuCl2, CuSO4 and Cu(Gly)2 with a similar degree. The particle size of hIAPP aggregates was decreased, which was further confirmed in atomic force microscopy (AFM) and transmission electron microscopy (TEM) images. Moreover, approximative cytotoxicity-enhancing levels between CuCl2, CuSO4 and Cu(Gly)2 on hIAPP were also observed in INS-1 cells. Studies on the action mechanisms displayed that copper compounds increased hIAPP-induced cytotoxicity by facilitating apoptosis-promoting effect of hIAPP, which was dominated mainly by cation. Furthermore, Cu(II)-promoted ROS overproduction and mitochondrial disruption might be the main reason for the enhanced apoptosis. Taken together, our studies demonstrate clear interaction mechanisms of Cu(II) and hIAPP in pancreatic beta cells, and provide useful information for our understanding and treatment of T2DM.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Synthesis, anticancer activity and toxicity of a water-soluble
           4S,5S-derivative of heptaplatin,
           
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Weiping Liu , Jing Jiang , Chengying Xie , Shuqian Hou , Haitian Quan , Qingsong Ye , Liguang Lou
      A water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]·(3-hydroxyl-cyclobutane-1,1-dicarboxylate)} was synthesized. The anticancer activity and toxicity were evaluated by comparing its interaction with DNA, cytotoxicity against four human cancer cell lines, antitumor efficiency in human gastric carcinoma NCI-N87 xenografts in nude mice, and preliminary side-effects in rats to those of its 4R,5R-optical isomer which is under preclinical development. Both isomers induce condensation of DNA to the same extent and have similar cytotoxicity, but show different antitumor activity and toxicity, probably owing to the difference in respective pharmacokinetic profiles. 4S,5S-Isomer seems to exhibit superior antitumor activity and less toxicity than 4R,5R-optical isomer as well as the parent heptaplatin. These results imply that 4S,5S-configuration as a new drug candidate may be better than 4R,5R-counterpart.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Editorial Board
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139




      PubDate: 2014-08-01T23:10:38Z
       
  • Contents
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139




      PubDate: 2014-08-01T23:10:38Z
       
  • Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential
           anticancer agents
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Artak Tovmasyan , Nelli Babayan , David Poghosyan , Kristine Margaryan , Boris Harutyunyan , Rusanna Grigoryan , Natalia Sarkisyan , Ivan Spasojevic , Suren Mamyan , Lida Sahakyan , Rouben Aroutiounian , Robert Ghazaryan , Gennadi Gasparyan
      In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characterized by UV–visible, electrospray ionization mass spectrometry (ESI-MS), 1H NMR techniques, lipophilicity (thin-layer chromatographic retention factor, R f), and elemental analysis. The key toxicological profile (i.e. cytotoxicity and cell line- (cancer type-) specificity; genotoxicity; cell cycle effects) of amphiphilic Ag porphyrin was studied in human normal and cancer cell lines of various tissue origins and compared with its water-soluble analog. Structural modification of the molecule from water-soluble to amphiphilic resulted in a certain increase in the cytotoxicity and a decrease in cell line-specificity. Importantly, Ag(II) porphyrin showed less toxicity to normal cells and greater toxicity to their cancerous counterparts as compared to cisplatin. The amphiphilic complex was also not genotoxic and demonstrated a slight cytostatic effect via the cell cycle delay due to the prolongation of S-phase. As expected, the performed structural modification affected also the photocytotoxic activity of metal-free amphiphilic porphyrin. The ligand tested on cancer cell line revealed a dramatic (more than 70-fold) amplification of its phototoxic activity as compared to its water-soluble tetracationic metal-free analog. The compound combines low dark cytotoxicity with 5 fold stronger phototoxicity relative to Chlorin e6 and could be considered as a potential photosensitizer for further development in photodynamic therapy.
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      PubDate: 2014-08-01T23:10:38Z
       
  • Evaluation of the Debye temperature for iron cores in human liver ferritin
           and its pharmaceutical analogue, Ferrum Lek, using Mössbauer
           spectroscopy
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): S.M. Dubiel , J. Cieślak , I.V. Alenkina , M.I. Oshtrakh , V.A. Semionkin
      An iron–polymaltose complex, Ferrum Lek, used as antianemic drug and considered as a ferritin analogue and human liver ferritin were investigated in the temperature range of 295–90K using 57Fe Mössbauer spectroscopy with a high velocity resolution (in 4096 channels). This study aimed to make a comparison of the Fe atom dynamics in the Ferrum Lek and ferritin iron cores by means of evaluation of the Debye temperature using the temperature dependence of the spectral center shift obtained with two different fitting procedures and the second order Doppler shift approach. The Debye temperature, evaluated as ΘD =502±24K for Ferrum Lek and ΘD =461±16K for human liver ferritin, demonstrated a very small difference in the Fe atom vibrations, reflecting a slightly smaller rigidity in the iron cores in human liver ferritin.
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      PubDate: 2014-08-01T23:10:38Z
       
  • Synthesis, structural characterization and cytotoxic activity of ternary
           copper(II)–dipeptide–phenanthroline complexes. A step towards
           the development of new copper compounds for the treatment of cancer
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Sebastián Iglesias , Natalia Alvarez , María H. Torre , Eduardo Kremer , Javier Ellena , Ronny R. Ribeiro , Rafael P. Barroso , Antonio J. Costa-Filho , M. Gabriela Kramer , Gianella Facchin
      In the search for new compounds with antitumor activity, coordination complexes with different metals are being studied by our group. This work presents the synthesis and characterization of six copper complexes with general stoichiometry [Cu(L-dipeptide)(phen)]·nH2O (were phen=1,10-phenanthroline) and their cytotoxic activities against tumor cell lines. To characterize these systems, analytical and spectroscopic studies were performed in solid state (by UV–visible, IR, X-ray diffraction) including the crystal structure of four new complexes (of the six complexes studied): [Cu(Ala-Phe)(phen)]·4H2O, [Cu(Phe-Ala)(phen)]·4H2O, [Cu(Phe-Val)(phen)]·4.5H2O and [Cu(Phe-Phe)(phen)]·3H2O. In all of them, the copper ion is situated in a distorted squared pyramidal environment. The phen ligand is perpendicular to the dipeptide, therefore exposed and potentially available for interaction with biological molecules. In addition, for all the studied complexes, structural information in solution using EPR and UV–visible spectroscopies were obtained, showing that the coordination observed in solid state is maintained. The lipophilicity, DNA binding and albumin interaction were also studied. Biological experiments showed that all the complexes induce cell death in the cell lines: HeLa (human cervical adenocarcinoma), MCF-7 (human metastatic breast adenocarcinoma) and A549 (human lung epithelial carcinoma). Among the six complexes, [Cu(Ala-Phe)(phen)] presents the lowest IC50 values. Taken together all these data we hypothesize that [Cu(Ala-Phe)(phen)] may be a good candidate for further studies in vivo.
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      PubDate: 2014-07-27T22:37:22Z
       
  • 8-Hydroxyquinoline Schiff-base compounds as antioxidants and modulators of
           copper-mediated Aβ peptide aggregation
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Luiza M.F. Gomes , Rafael P. Vieira , Michael R. Jones , Michael C.P. Wang , Christine Dyrager , Elaine M. Souza-Fagundes , Jeferson G. Da Silva , Tim Storr , Heloisa Beraldo
      One of the hallmarks of Alzheimer's disease (AD) in the brain are amyloid-β (Aβ) plaques, and metal ions such as copper(II) and zinc(II) have been shown to play a role in the aggregation and toxicity of the Aβ peptide, the major constituent of these extracellular aggregates. Metal binding agents can promote the disaggregation of Aβ plaques, and have shown promise as AD therapeutics. Herein, we describe the syntheses and characterization of an acetohydrazone (8-H2QH), a thiosemicarbazone (8-H2QT), and a semicarbazone (8-H2QS) derived from 8-hydroxyquinoline. The three compounds are shown to be neutral at pH7.4, and are potent antioxidants as measured by a Trolox Equivalent Antioxidant Capacity (TEAC) assay. The ligands form complexes with CuII, 8-H2QT in a 1:1 metal:ligand ratio, and 8-H2QH and 8-H2QS in a 1:2 metal:ligand ratio. A preliminary aggregation inhibition assay using the Aβ1–40 peptide showed that 8-H2QS and 8-H2QH inhibit peptide aggregation in the presence of CuII. Native gel electrophoresis/Western blot and TEM images were obtained to give a more detailed picture of the extent and pathways of Aβ aggregation using the more neurotoxic Aβ1−42 in the presence and absence of CuII, 8-H2QH, 8-H2QS and the drug candidate PBT2. An increase in the formation of oligomeric species is evident in the presence of CuII. However, in the presence of ligands and CuII, the results match those for the peptide alone, suggesting that the ligands function by sequestering CuII and limiting oligomer formation in this assay.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Comparison of oxygen-induced radical intermediates in iNOS oxygenase
           domain with those from nNOS and eNOS
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Vladimír Berka , Wen Liu , Gang Wu , Ah-Lim Tsai
      Inducible nitric-oxide synthase (iNOS) produces the reactive oxygen and nitrogen species (ROS/RNS) involved in bacteria killing and is crucial in the host defense mechanism. However, high level ROS/RNS can also be detrimental to normal cells and thus their production has to be tightly controlled. Availability or deficiency of tetrahydrobiopterin (BH4) cofactor and l-arginine substrate controls coupling or uncoupling of NOS catalysis. Fully coupled reaction, with abundant BH4 and l-arginine, produces NO whereas the uncoupled NOS (in the absence of BH4 and/or l-arginine) generates ROS/RNS. In the current work we focus on direct rapid freeze EPR to characterize the structure and kinetics of oxygen-induced radical intermediates produced by ferrous inducible NOS oxygenase domain (iNOSox) in the presence or absence of BH4 and/or l-arginine. Fully reconstituted iNOSox (+BH4, +L-Arg) forms a dimer and yields a typical BH4 radical that indicates coupled reaction. iNOSox (−BH4) remains mainly monomeric and produces exclusively superoxide, that is only marginally affected by the presence of l-arginine. iNOSox (+BH4, −L-Arg) exists as a monomer/dimer mixture and yields both BH4 radical and superoxide. Present study is a natural extension of our previous work on the ferrous endothelial NOSox (eNOSox) [V. Berka, G. Wu, H.C. Yeh, G. Palmer, A.L. Tsai, J. Biol. Chem. 279 (2004) 32243–32251] and ferrous neuronal NOSox (nNOSox) [V. Berka, L.H. Wang, A.L. Tsai, Biochemistry 47 (2008) 405–420]. Overall, our data suggests different regulatory roles of l-arginine and BH4 in the production of oxygen-induced radical intermediates in NOS isoforms which nicely serve individual functional role.
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      PubDate: 2014-07-27T22:37:22Z
       
  • In vitro antibacterial activity of meclofenamate metal complexes with
           Cd(II), Pb(II), Co(II), and Cu(II). Crystal structures of
           [Cd(C14H10NO2Cl2)2∙(CH3OH)]n and [Cu(C14H10NO2Cl2)2(C5H5N)2]
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): T. Palacios-Hernández , H. Höpfl , J.L. Sánchez-Salas , E. González-Vergara , A. Pérez-Benítez , M.A. Quiroz-Alfaro , M.A. Méndez-Rojas
      The synthesis and characterization of five metal complexes derived from sodium meclofenamate (1) are reported: [Cd(C14H10NO2Cl2)2∙(CH3OH)]n∙nCH3OH (6), [Pb(C14H10NO2Cl2)2]n (7), [Co(C14H10NO2Cl2)]n (8), [Cu(C14H10NO2Cl2)]n (9), and [Cu(C14H10NO2Cl2)2(C5H5N)2] (10) (C14H10NO2Cl2 =meclofenamate; C5H5N=pyridine). The characterization of the compounds was based on FTIR and UV–visible spectroscopy, mass spectrometry and, in the case of complexes 6 and 10, single crystal X-ray diffraction analysis. For compound 6, the structural analysis revealed a 1-D polymeric chain structure, in which pentagonal planar [Cd(RCOO)2(CH3OH)] units were linked through bridging carboxylate functions of the meclofenamate ligands. The overall coordination environment of the Cd(II) ions was seven-coordinate, since each carboxylate group exhibited a μ3-bridging coordination mode. On the other hand, for complex 10 a discrete mononuclear structure was observed, in which the six-coordinate copper(II) metal atoms were coordinated by two pyridine molecules and the carboxylate functions of two meclofenamate entities, in an anisobidentate coordination mode. The antibacterial activity of compounds 6–9 against four strains of Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacteria was examined, finding that only complex 6 was active. Additionally, it was found that the Co(II) and Cu(II) complexes 8 and 9 showed peroxidase activity.
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      PubDate: 2014-07-27T22:37:22Z
       
  • A monofunctional trinuclear platinum complex with steric hindrance
           demonstrates strong cytotoxicity against tumor cells
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Shangnong Wu , Xiaoyong Wang , Yafeng He , Zhenzhu Zhu , Chengcheng Zhu , Zijian Guo
      Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by 1H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by 1H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Mn(II)/Mn(III) and Fe(III) binding capability of two Aspergillus fumigatus
           siderophores, desferricrocin and N′, N″,
           N‴-triacetylfusarinine C
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Etelka Farkas , Orsolya Szabó , Péter L. Parajdi-Losonczi , György Balla , István Pócsi
      Manganese(II) and manganese(III) complexes of the exocyclic desferricrocin (H3DFCR) and endocyclic triacetylfusarinine C (H3TAF) in solution have been studied by using pH-potentiometry, UV–Vis spectrophotometry, relaxometry and cyclic voltammetry. A comparison between the present results and the corresponding ones for the open-chain analogues, desferrioxamine B (DFB) and desferricoprogen (DFC), shows (i) The dissociation processes of H3DFCR occur in the expected pH-range (pH7–10.5), but hydrogen bonding is assumed to be responsible for a quite low proton dissociation constant (pK=4.18) of H3TAF and also an unusually high one (10.59). (ii) Moderate stability complexes with 1:1 Mn(II) to ligand ratio are formed with all four siderophores. (iii) The coordination of the three hydroxamates of a siderophore takes place in stepwise processes, except the case of desferricrocin, with which, large-extent overlapping of the processes occurs. (iv) Out of the four tris-chelated [ML] type complexes, the complex of DFCR is the most compact, as it is indicated by the relaxivity values. (v) Following the stoichiometric oxidation of the Mn(II)–siderophore complexes at pH≥9, tris-chelated Mn(III) complexes are formed. To make a comparison between the stability of the Mn(III) and the corresponding Fe(III) complexes of DFCR and TAF, the determination of the stability of the Fe(III) complexes under our condition has also been performed, by using UV–Vis spectrophotometry. Comparable stability of the corresponding complexes was found. (vi) Correlation study of the stability constants resulted in estimation of the constant of the Mn(III) monohydroxo complex, for which there was no data in the literature under our conditions.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Mechanistic basis for the enantioselectivity of the anaerobic
           hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Maciej Szaleniec , Agnieszka Dudzik , Bartłomiej Kozik , Tomasz Borowski , Johann Heider , Małgorzata Witko
      The enantioselectivity of reactions catalyzed by ethylbenzene dehydrogenase, a molybdenum enzyme that catalyzes the oxygen-independent hydroxylation of many alkylaromatic and alkylheterocyclic compounds to secondary alcohols, was studied by chiral chromatography and theoretical modeling. Chromatographic analyses of 22 substrates revealed that this enzyme exhibits remarkably high reaction enantioselectivity toward (S)-secondary alcohols (18 substrates converted with >99% ee). Theoretical QM:MM modeling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. This analysis showed that the enzyme imposes strong stereoselectivity on the reaction by discriminating the hydrogen atom abstracted from the substrate. Activation of the pro(S) hydrogen atom was calculated to be 500 times faster than of the pro(R) hydrogen atom. The actual hydroxylation step (i.e., hydroxyl group rebound reaction to a carbocation intermediate) does not appear to be enantioselective enough to explain the experimental data (the calculated rate ratios were in the range of only 2–50 for pro(S): pro(R)-oriented OH rebound).
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      PubDate: 2014-07-27T22:37:22Z
       
  • Cyclopalladated and cycloplatinated benzophenone imines: Antitumor,
           antibacterial and antioxidant activities, DNA interaction and cathepsin B
           inhibition
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Joan Albert , Lucía D'Andrea , Jaume Granell , Pepita Pla-Vilanova , Josefina Quirante , Muhammad Kaleem Khosa , Carme Calvis , Ramon Messeguer , Josefa Badía , Laura Baldomà , Mercè Font-Bardia , Teresa Calvet
      The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans- N , P -[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1–4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1–4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1–5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1–2 and 4–5 presented also antioxidant activity. Compounds 1–5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato
           ligands
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Vojtech Novohradsky , Lenka Zerzankova , Jana Stepankova , Oldrich Vrana , Raji Raveendran , Dan Gibson , Jana Kasparkova , Viktor Brabec
      We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin conjugated with valproic acid (VPA), a well-known drug having histone deacetylase inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the conjugates was lower in cell culture than that of oxaliplatin, but greater than those of its Pt(IV) derivative containing biologically inactive axial ligands in several cancer cell lines. Notably, these conjugates display activity in both cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced accumulation in tumor cells and acting in a dual threat manner, concurrently targeting histone deacetylase and genomic DNA. These results demonstrate the dual targeting strategy to be a valuable route to pursue in the design of platinum agents which may be more effective in cancer types that are typically resistant to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives containing VPA axial ligands seem to be promising dual-targeting candidates for additional preclinical studies.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Two structurally analogous ruthenium complexes as naked-eye and reversible
           molecular “light switch” for G-quadruplex DNA
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Xiao-Hui Lu , Shuo Shi , Jun-Liang Yao , Xing Gao , Hai-Liang Huang , Tian-Ming Yao
      A pair of symmetrical furyl based ruthenium(II) complexes ([Ru(phen)2dpq-df]2+ (1) and [Ru(bpy)2dpq-df]2+ (2) (phen=1,10-phenanthroline, bpy=2,2′-bipyridine, dpq-df=dipyrido (3,2-a:2′,3′-c) quinoxaline-difuran) have been prepared and characterized. The binding properties of both complexes toward G-quadruplex DNA have been investigated by fluorescence spectroscopy, UV–Vis spectroscopy, circular dichroism (CD), fluorescence resonance energy transfer (FRET) melting assays and molecular docking studies. The experimental results indicated that both Ru-complexes exhibited a remarkable “light switch” effect in the presence of hybrid G-quadruplex DNA. Interestingly, the “light switch” can be repeated off and on through the successive addition of Cu2+ ions and EDTA, and all these behaviors can be observed even by the naked eyes. Moreover, FRET melting assay revealed that both complexes could be potential stabilizers for G-quadruplex architectures. The computational studies not only confirmed that the two complex molecules bound to one G-quadruplex DNA molecule, but also explained the “light switch” effect.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Metal-binding and redox properties of substituted linear and cyclic ATCUN
           motifs
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Kosh P. Neupane , Amanda R. Aldous , Joshua A. Kritzer
      The amino-terminal copper and nickel binding (ATCUN) motif is a short peptide sequence found in human serum albumin and other proteins. Synthetic ATCUN–metal complexes have been used to oxidatively cleave proteins and DNA, cross-link proteins, and damage cancer cells. The ATCUN motif consists of a tripeptide that coordinates Cu(II) and Ni(II) ions in a square planar geometry, anchored by chelation sites at the N-terminal amine, histidine imidazole and two backbone amides. Many studies have shown that the histidine is required for tight binding and square planar geometry. Previously, we showed that macrocyclization of the ATCUN motif can lead to high-affinity binding with altered metal ion selectivity and enhanced Cu(II)/Cu(III) redox cycling (Inorg. Chem. 2013, 52, 2729–2735). In this work, we synthesize and characterize several linear and cyclic ATCUN variants to explore how substitutions at the histidine alter the metal-binding and catalytic properties. UV–visible spectroscopy, EPR spectroscopy and mass spectrometry indicate that cyclization can promote the formation of ATCUN-like complexes even in the absence of imidazole. We also report several novel ATCUN-like complexes and quantify their redox properties. These findings further demonstrate the effects of conformational constraints on short, metal-binding peptides, and also provide novel redox-active metallopeptides suitable for testing as catalysts for stereoselective or regioselective oxidation reactions.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Occupational exposure to aluminum and its amyloidogenic link with
           cognitive functions
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): N.H. Zawilla , F.M. Taha , N.A. Kishk , S.A. Farahat , M. Farghaly , M. Hussein
      As many other metals, aluminum is a widely recognized neurotoxicant and its link with neurodegenerative disorders has been the subject of scientific debate. One proposal focuses on amyloid β deposition (amyloidogenesis) as the key player in triggering neuronal dysfunction the so-called amyloid cascade hypothesis. We undertook this study first to investigate the cognition status of workers exposed to Al dust in an Al factory in Southern Cairo, second, to evaluate serum amyloid precursor protein (APP) and cathepsin D (CD) enzyme activity to study the possible role of Al in amyloidogenesis, and finally to explore the relation between these potential biomarkers and cognitive functions. The study was conducted on 54 exposed workers and 51 matched controls. They were subjected to questionnaire, neurological examination and a cognitive test battery, Addenbrooke's Cognitive Examination — Revised (ACE-R). Serum Al, APP and CD enzyme activity were measured. A significant increase of serum Al was found in the exposed workers with an associated increase in serum APP and decrement in CD activity. The exposed workers displayed poor performance on the ACE-R test. No significant correlation was detected between ACE-R test total score and either APP or CD activity. We concluded that occupational exposure to Al is associated with cognitive impairment. The effect of occupational Al exposure on the serum levels of APP and CD activity may be regarded as a possible mechanism of Al in amyloidogenesis. However, our findings do not support the utility of serum APP and CD activity as screening markers for early or preclinical cognitive impairment.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Copper(II), nickel(II) and zinc(II) complexes of the N-terminal
           nonapeptide fragment of amyloid-β and its derivatives
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Ágnes Grenács , Imre Sóvágó
      Copper(II), nickel(II) and zinc(II) complexes of the nonapeptide fragment of amyloid-β Aβ(1–9) (NH2-DAEFRHDSG-NH2) and its two derivatives: NH2-DAAAAHAAA-NH2 and NH2-DAAAAAHAA-NH2 have been studied by potentiometric, UV–visible and CD spectroscopic methods. The results reveal the primary role of the amino terminus of peptides in copper(II) and nickel(II) binding. The formation of dinuclear complexes was also possible in the copper(II) containing systems but only the first six amino acids from the amino terminus were involved in metal binding in the physiologically relevant pH range. The coordination chemistry of the two alanine mutated peptides is almost the same as that of the native nonapeptide, but the thermodynamic stability of the copper(II) complexes of the mutants is significantly reduced. This difference probably comes from the secondary interactions of the polar side chains of Asp, Glu, Ser and Arg residues present in the native peptide. Moreover, this difference reveals that the amino acid sequence of the N-terminal domains of amyloid peptides is especially well suited for the complexation with copper(II) ions.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis, characterization and binding affinities of rhenium(I)
           thiosemicarbazone complexes for the estrogen receptor (α/β)
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Ara Núñez-Montenegro , Rosa Carballo , Ezequiel M. Vázquez-López
      The binding affinities towards estrogen receptors (ERs) α and β of a set of thiosemicarbazone ligands (HLn) and their rhenium(I) carbonyl complexes [ReX(HLn)(CO)3] (X=Cl, Br) were determined by a competitive standard radiometric assay with [3H]-estradiol. The ability of the coordinated thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX bond were used as a synthetic strategy to obtain [Re(hpy)(Ln)(CO)3] (hpy=3- or 4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new thiosemicarbazonate complexes with an improved affinity towards the estrogen receptors and, consequently, the values of the inhibition constant (Ki) could be determined for some of them. In general, the values of Ki for both ER subtypes suggest an appreciable selectivity towards ERα.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis and properties of a new micellar
           polyphosphazene–platinum(II) conjugate drug
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Prakash G. Avaji , Hye In Joo , Jung Hyun Park , Kyung Su Park , Yong Joo Jun , Hwa Jeong Lee , Youn Soo Sohn
      Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(±)-1,2-diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene backbone. This monomeric Pt-complex could easily be grafted to the PEGylated polyphosphazene backbone to prepare a novel polyphosphazene–Pt conjugate, [NP(MPEG550)(dach)Pt(EM)]n [MPEG550: methoxy poly(ethylene glycol) with an average molecular weight of 550; EM: ethoxymalate]. This amphiphilic polyphosphazene–Pt conjugate was found to self-assemble into stable polymeric micelles of a mean diameter of 130nm, which is suitable for passive tumor targeting by enhanced permeability and retention (EPR) effect. Pharmacokinetic study of this polymer conjugate exhibited long blood circulation as expected and longer half-life (t1/2β=9.52h) compared with oxaliplatin (3.47h), and much larger AUC (area under the curve) value (25,831ng·h/mL) compared with oxaliplatin (1194ng·h/mL). Biodistribution study of the polymer conjugate has shown excellent tumor selectivity with the tumor to tissue ratio of 3.84 at 2h post injection and 11.7 at 24h post injection probably due to the EPR effect of the polymer conjugate while no tumor selectivity was observed for monomeric oxaliplatin. Furthermore, accumulation of this polymer conjugate in kidney was much lower compared with oxaliplatin. Also the nude mouse xenograft trial of the polymer conjugate has shown higher antitumor efficacy compared with oxaliplatin.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Curcumin derivatives as metal-chelating agents with potential
           multifunctional activity for pharmaceutical applications
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Erika Ferrari , Rois Benassi , Stefania Sacchi , Francesca Pignedoli , Mattia Asti , Monica Saladini
      Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga3+, Cu2+) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto–enol form. The formation of metal complexes is followed by both NMR and UV–vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga3+ and Cu2+ are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2]+ was found more stable than curcumin one. Good agreement is detected between calculated and experimental 1H and 13C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga3+ complexes display possible superoxide dismutase (SOD)-like activity.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Cellular uptake and cytotoxicity of a near-IR fluorescent
           corrole–TiO2 nanoconjugate
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Carl M. Blumenfeld , Bryce F. Sadtler , G. Esteban Fernandez , Lily Dara , Cathie Nguyen , Felix Alonso-Valenteen , Lali Medina-Kauwe , Rex A. Moats , Nathan S. Lewis , Robert H. Grubbs , Harry B. Gray , Karn Sorasaenee
      We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole–TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al–TiO2) was prepared. The nanoparticle 1-Al–TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29nm for 1-Al–TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20–40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al–TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al–TiO2 was found inside the cancer cells even at low doses (0.02–2μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al–TiO2 showed minimal cytotoxic effects even at higher doses (2–2000μg/mL) after 24h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al–TiO2 at low doses (0.0003–3μg/mL). Longer incubation times (after 48 and 72h for U87-Luc) and higher doses (>20μg/mL 1-Al–TiO2 for U87-Luc and >3μg/mL 1-Al–TiO2 for PMH) showed decreased cell viability.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • A rhodium(III) complex inhibits LPS-induced nitric oxide production and
           angiogenic activity in cellulo
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Li-Juan Liu , Sheng Lin , Daniel Shiu-Hin Chan , Chi Teng Vong , Pui Man Hoi , Chun-Yuen Wong , Dik-Lung Ma , Chung-Hang Leung
      Metal-containing complexes have arisen as viable alternatives to organic molecules as therapeutic agents. Metal complexes possess a number of advantages compared to conventional carbon-based compounds, such as distinct geometries, interesting electronic properties, variable oxidation states and the ability to arrange different ligands around the metal centre in a precise fashion. Meanwhile, nitric oxide (NO) plays key roles in the regulation of angiogenesis, vascular permeability and inflammation. We herein report a novel cyclometalated rhodium(III) complex as an inhibitor of lipopolysaccharides (LPS)-induced NO production in RAW264.7 macrophages. Experiments suggested that the inhibition of NO production in cells by complex 1 was mediated through the down-regulation of nuclear factor-κB (NF-κB) activity. Furthermore, complex 1 inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs) as revealed by an endothelial tube formation assay. This study demonstrates that kinetically inert rhodium(III) complexes may be potentially developed as effective anti-angiogenic agents.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Introduction of water into the heme distal side by Leu65 mutations of an
           oxygen sensor, YddV, generates verdoheme and carbon monoxide, exerting the
           heme oxygenase reaction
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Martin Stranava , Markéta Martínková , Marie Stiborová , Petr Man , Kenichi Kitanishi , Lucie Muchová , Libor Vítek , Václav Martínek , Toru Shimizu
      The globin-coupled oxygen sensor, YddV, is a heme-based oxygen sensor diguanylate cyclase. Oxygen binding to the heme Fe(II) complex in the N-terminal sensor domain of this enzyme substantially enhances its diguanylate cyclase activity which is conducted in the C-terminal functional domain. Leu65 is located on the heme distal side and is important for keeping the stability of the heme Fe(II)–O2 complex by preventing the entry of the water molecule to the heme complex. In the present study, it was found that (i) Escherichia coli-overexpressed and purified L65N mutant of the isolated heme-bound domain of YddV (YddV-heme) contained the verdoheme iron complex and other modified heme complexes as determined by optical absorption spectroscopy and mass spectrometry; (ii) CO was generated in the reconstituted system composed of heme-bound L65N and NADPH:cytochrome P450 reductase as confirmed by gas chromatography; (iii) CO generation of heme-bound L65N in the reconstituted system was inhibited by superoxide dismutase and catalase. In a concordance with the result, the reactive oxygen species increased the CO generation; (iv) the E. coli cells overexpressing the L65N protein of YddV-heme also formed significant amounts of CO compared to the cells overexpressing the wild type protein; (v) generation of verdoheme and CO was also observed for other mutants at Leu65 as well, but to a lesser extent. Since Leu65 mutations are assumed to introduce the water molecule into the heme distal side of YddV-heme, it is suggested that the water molecule would significantly contribute to facilitating heme oxygenase reactions for the Leu65 mutants.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • High metal substitution tolerance of anthrax lethal factor and
           characterization of its active copper-substituted analogue
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Suet Y. Lo , Crystal E. Säbel , Michael I. Webb , Charles J. Walsby , Stefan Siemann
      Anthrax lethal factor (LF) is a zinc-dependent metalloendopeptidase and a member of the gluzincin family. The current report demonstrates a high metal substitution tolerance of LF atypical of gluzincins and other zinc-dependent metalloproteases. Mn2+, Co2+, Ni2+, Cu2+ and Cd2+ were found to reactivate the apoprotein of LF to a level either comparable to or significantly higher than that noted for the native zinc enzyme. The most active form of LF was obtained with Cu2+, a surprising observation since most Cu2+-substituted zinc proteases display very low activity. Cu2+-substituted LF (CuLF), prepared by direct exchange and by apoprotein reconstitution methodologies, displayed a several-fold higher catalytic competence towards chromogenic and fluorogenic LF substrates than native LF. CuLF bound Cu2+ tightly with a dissociation constant in the femtomolar range. The electron paramagnetic resonance spectrum of CuLF revealed the protein-bound metal ion to be coordinated to two nitrogen donor atoms, suggesting that Cu2+ binds to both active site histidine residues. While ZnLF and CuLF (prepared by direct exchange) were capable of killing RAW 264.7 murine macrophage-like cells, apoLF and all metal-reconstituted apoprotein preparations failed to elicit a cytotoxic response. Competition experiments using apoLF/ZnLF mixtures demonstrated the propensity of apoLF to relieve ZnLF-induced cell death, suggesting that both protein forms can compete with each other for binding to protective antigen. The lack of cytotoxicity of apoLF and its metal-reconstituted variants likely originates from structural perturbations in these proteins which might prevent their translocation into the cytoplasm.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Proton pumping by an inactive structural variant of cytochrome c oxidase
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Emelie Svahn , Kristina Faxén , Robert B. Gennis , Peter Brzezinski
      The aa 3-type cytochrome c oxidases (CytcOs) from e.g. Rhodobacter sphaeroides and Paracoccus denitrificans harbor two proton-transfer pathways. The K pathway is used for proton uptake upon reduction of the CytcO, while the D pathway is used after binding of O2 to the catalytic site. The aim of the present study was to determine whether or not CytcO in which the K pathway is blocked (by e.g. the Lys362Met replacement) is capable of pumping protons. The process can not be studied using conventional assays because the O2-reduction activity is too low when the K pathway is blocked. Consequently, proton pumping with a blocked K pathway has not been demonstrated directly. Here, the Lys362Met and Ser299Glu structural variants were reconstituted in liposomes and allowed to (slowly) become completely reduced. Then, the reaction with O2 was studied with μs time resolution after flash photolysis of a blocking CO ligand bound to heme a 3. The data show that with both the inactive Lys362Met and partly active Ser299Glu variants proton release occurred with the same time constants as with the wild-type oxidase, i.e. ~200μs and ~3ms, corresponding in time to formation of the ferryl and oxidized states, respectively. Thus, the data show that the K pathway is not required for proton pumping, suggesting that D and K pathways operate independently of each other after binding of O2 to the catalytic site.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Light-stable bis(norharmane)silver(I) compounds: Synthesis,
           characterization and antiproliferative effects in cancer cells
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Rais Ahmad Khan , Khalid Al-Farhan , Andreia de Almeida , Ali Alsalme , Angela Casini , Mohamed Ghazzali , Jan Reedijk
      Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4 −, NO3 − and BF4 −) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6 − anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375nm, when excited at 290nm.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Interaction of Pd2+ complexes of 2,6-disubstituted pyridines with
           nucleoside 5´-monophosphates
    • Abstract: Publication date: Available online 5 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Oleg Golubev , Tuomas Lönnberg , Harri Lönnberg
      To learn more about the underlying principles of metal-ion-mediated recognition of nucleic acid bases, PdCl+ complexes of six 2,6-disubstituted pyridines, viz. pyridine-2,6-dicarboxamide, its N 2,N 6-dimethyl and N 2,N 6-diisopropyl derivatives, 6-carbamoylpyridine-2-carboxylic acid, 6-aminomethylpyridine-2-carboxamide and its N 2-methyl derivative, were prepared and their interaction with nucleoside 5´-monophosphate (NMP) was studied by 1H NMR spectroscopy in D2O at pH7.2. The binding sites within the nucleobases were assigned on the basis of Pd2+ induced changes in chemical shifts of the base moiety proton resonances. The mole fractions of NMPs engaged in mono- or dinuclear Pd2+ complexes were determined at various concentrations by comparing the intensities of the aromatic and anomeric protons of the complexed and uncomplexed NMPs. Some of the pyridine complexes showed moderate discrimination between the NMPs.
      Graphical abstract image Highlights To learn more about the underlying principles of metal-ion-mediated recognition of nucleic acid bases, PdCl+ complexes of six 2,6-disubstituted pyridines were prepared and their interaction with nucleoside 5´-monophosphate (NMP) was studied by 1H NMR spectroscopy in D2O at pH7.2.

      PubDate: 2014-06-09T15:50:10Z
       
  • The impact of synthetic analogs of histidine on copper(II) and nickel(II)
           coordination properties to an albumin-like peptide. Possible leads towards
           new metallodrugs
    • Abstract: Publication date: Available online 2 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Izabela Zawisza , Mariusz Mital , Agnieszka Polkowska-Nowakowska , Arkadiusz Bonna , Wojciech Bal
      The purpose of our research was to obtain peptidomimetics possessing Cu(II) and Ni(II) binding properties, which would be useful for biomedical applications. In this context we used potentiometry, UV-VIS and CD spectroscopies to characterize the Cu(II) and Ni(II) binding properties of pentapeptide analogs of the N-terminal sequence of histatin 5. The peptides investigated had a general sequence DSXAK-am (am stands for C-terminal amide), with X including His and its three synthetic analogs, (4-thiazolyl)-L-alanine (1), (2-pyridyl)-L-alanine (2), and (pyrazol-1-yl)-L-alanine (3). The heterocyclic nitrogens present in these analogs were significantly more acidic than that of the His imidazole. We found that DSXAK-am peptides were able to bind Cu(II) and Ni(II) and form 4N complexes in a cooperative fashion, with similar affinities. These results indicate that acidic heterocyclic amino acids provide a viable alternative for histidine in peptidomimetics designed for metal ions binding.
      Graphical abstract image

      PubDate: 2014-06-03T14:58:10Z
       
 
 
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