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  Subjects -> CHEMISTRY (Total: 765 journals)
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INORGANIC CHEMISTRY (40 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 18)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 10)
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: 5)
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: 4)
Inorganic Chemistry     Full-text available via subscription   (Followers: 18)
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: 3)
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: 6)
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
   [5 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]
  • A.SigelH.SigelR.K.O.SigelInterrelations between Essential Metal Ions and
           Human DiseasesMetal Ions in Life Sciencesvol.
           132013SpringerDordrecht978-94-007-7499-5
    • Abstract: Publication date: Available online 8 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Hui Chao



      PubDate: 2014-06-09T15:50:10Z
       
  • 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
       
  • Contents
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137




      PubDate: 2014-06-09T15:50:10Z
       
  • Decavanadate in vitro and in vivo effects: facts and opinions
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): M. Aureliano , C. André Ohlin
      This review covers recent advances in the understanding of the in vitro and in vivo effects of decavanadate, (V10O28)6−, particularly in mitochondria. In vivo toxicological studies involving vanadium rarely account for the fact that under physiological conditions some vanadium may be present in the form of the decavanadate ion, which may behave differently from ortho- and metavanadates. It has for example been demonstrated that vanadium levels in heart or liver mitochondria are increased upon decavanadate exposure. Additionally, in vitro studies have shown that mitochondrial depolarization (IC50, 40 nM) and oxygen consumption (IC50, 99 nM) are strongly affected by decavanadate, which causes reduction of cytochrome b (complex III). We review these recent findings which together suggest that the observed cellular targets, metabolic pathway and toxicological effects differ according to the species of vanadium present. Finally, the toxicological effects of decavanadate depend on several factors such as the mode of administration, exposure time and type of tissue.
      Graphical abstract image

      PubDate: 2014-06-09T15:50:10Z
       
  • Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer
           naphthoquinone plumbagin with enhanced efficacy against resistant cancer
           cells and a genuine mode of action
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Cornelia Spoerlein-Guettler , Katharina Mahal , Rainer Schobert , Bernhard Biersack
      A series of ferrocene and (arene)ruthenium(II) complexes attached to the naturally occurring anticancer naphthoquinones plumbagin and juglone was tested for efficacy against various cancer cell lines and for alterations in the mode of action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and showed IC50 (72h) values around 1μM in growth inhibition assays using 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter cell line, for their substrate character for the P-glycoprotein drug eflux pump via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS levels were significantly increased upon treatment with 1c and 2a. These compounds also showed a greater affinity to linear DNA than plumbagin. While plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives 1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated calcein-AM efflux relative to the clinically established sensitizer verapamil.
      Graphical abstract image

      PubDate: 2014-06-09T15:50:10Z
       
  • Editorial Board
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137




      PubDate: 2014-06-09T15:50:10Z
       
  • Enantioselective DNA condensation induced by heptameric lanthanum helical
           supramolecular enantiomers
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Fei-Fei Bao , Xin-Xin Xu , Wen Zhou , Chun-Yan Pang , Zaijun Li , Zhi-Guo Gu
      DNA condensation induced by a pair of heptameric La(III) helical enantiomers M-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O and P-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O ( M -La and P -La, L=2-(2-hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and SEM. The enantiomers M -La and P -La could induce CT-DNA condensation at a low concentration as observed in UV/vis spectroscopy. DNA condensates possessed globular nanoparticles with nearly homogeneous sizes in solid state determined by SEM (ca. 250nm for M -La and ca. 200nm for P -La). The enantiomers bound to DNA through electrostatic attraction and hydrogen bond interactions in a major groove, and rapidly condensed free DNA into its compact state. DNA decompaction has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M -La and P -La displayed discernible discrimination in DNA interaction and DNA condensation, as well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M -La and P -La were efficient DNA packaging agents with potential applications in gene delivery.
      Graphical abstract image

      PubDate: 2014-06-09T15:50:10Z
       
  • Copper(II) Complexes of Alloferon 1 with Point Mutations (H1A) and (H9A)
           Stability Structure and Biological Activity
    • Abstract: Publication date: Available online 2 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Agnieszka Matusiak , Mariola Kuczer , Elżbieta Czarniewska , Grzegorz Rosiński , Teresa Kowalik-Jankowska
      Mono- and polynuclear copper(II) complexes of the alloferon 1 with point mutations (H1A) A1GVSGH6GQH9GVH12G (Allo1A) and (H9A) H1GVSGH6GQA9GVH12G (Allo9A) have been studied by potentiometric, UV-visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a complete complex speciation different metal-to-ligand molar ratios ranging from 1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His residue in first position of the peptide chain changes the coordination abilities of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N-terminal His residue of the Allo9A peptide forms stable 6-membered chelate with the terminal amino group. Furthermore, the presence of two additional histidine residues in the Allo9A peptide (H6,H12) leads to the formation of the CuL complex with 4N {NH2,NIm-H1,NIm-H6,NIm-H12} binding site in wide pH range (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at physiological pH7.4 the predominant complex the CuH-1 L consists of the 3N {NH2, N-,CO,NIm} coordination mode. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II) complexes displayed the lowest haemocytotoxic activity while the most active was the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N-terminal-His1 and His6 residues may be more important for their proapoptotic properties in insects than those at positions 9 and 12 in the peptide chain.
      Graphical abstract image

      PubDate: 2014-06-03T14:58:10Z
       
  • 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
       
  • A novel quinoline molecular probe and the derived functionalized gold
           nanoparticles: Sensing properties and cytotoxicity studies in MCF-7 human
           breast cancer cells
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Cristina Núñez , Elisabete Oliveira , Javier García-Pardo , Mario Diniz , Julia Lorenzo , José Luis Capelo , Carlos Lodeiro
      A highly selective quinoline-based fluorescent sensor L was designed, prepared and used to monitor zinc ions in Goldfish (Carassius auratus) as model of vertebrate organism. Modified gold nanoparticles having functional quinoline molecules (GNPs@L) were also synthesized and their sensing properties towards different metal ions were also explored in solution, showing high selectively towards the toxic and heavy metal ion mercury. Cell proliferation kit XTT that employs 2,3-bis-(2-methoxy-4-nitro- 5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) was used in order to investigate the cytotoxicity of compound L and GNPs@L on the MCF-7 breast cancer cells, showing significant cytotoxicity in comparison with similar reported systems. It was observed that L and GNPs@L compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM).
      Graphical abstract image

      PubDate: 2014-05-27T11:29:22Z
       
  • Anti-tumor activities of Au(I) complexed with bisphosphines in HL-60 cells
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Ryo Hayashi , Kazuhiro Nakatsui , Daisuke Sugiyama , Toshiki Kitajima , Nobuhiko Oohara , Masashi Sugiya , Satoshi Osada , Hiroaki Kodama
      We found that Au(I) complexed with 2,3-bis(tert-butyl(methyl)phosphino) quinoxaline (10) was a potent anti-tumor agent (half-maximal growth inhibitory concentration, GI50 =0.87μM) with broad anti-tumor activity. In particular, the activity of complex 10 was high in tumor cell lines derived from the colon and ovary. Treatment with complex 10 resulted in the apoptosis of HL-60 cells. The ligand for the preparation of complex 10 is commercially available implying that complex 10 might be a good drug candidate for cancer therapy.
      Graphical abstract image

      PubDate: 2014-05-27T11:29:22Z
       
  • Spectroscopic studies on HasA from Yersinia pseudotuberculosis
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Shin-ichi Ozaki , Takehiro Sato , Yukari Sekine , Catharina T. Migita , Takeshi Uchida , Koichiro Ishimori
      Heme acquisition system A (HasA) is known as a hemophore in Gram-negative pathogens. The ferric heme iron is coordinated by Tyr-75 and His-32 in holo-HasA from Pseudomonas aeruginosa (HasApa). In contrast, in holo-HasA from Yersinia pseudotuberculosis (HasAyp), our spectroscopic studies suggest that only Tyr-75 coordinates to the ferric heme iron. The substitution of Gln-32 with alanine in HasAyp does not alter the spectroscopic properties, indicating that Gln-32 is not an axial ligand for the heme iron. Somewhat surprisingly, the Y75A mutant of HasAyp can capture a free hemin molecule but the rate of hemin uptake is slower than that of wild type, suggesting that the hydrophobic interaction in the heme pocket may also play a role in heme acquisition. Unlike in wild type apoprotein, ferric heme transfer from Hb to Y75A apo-HasAyp has not been observed. These results imply that coordination (bonding/interaction) between Tyr-75 and the heme iron is important for heme transfer from Hb. Interestingly, HasAyp differs from HasApa in its ability to bind the ferrous heme iron. Apo-HasAyp can capture ferrous heme and resonance Raman spectra of ferrous-carbon monoxide holo-HasAyp suggest that Tyr-75 is protonated when the heme iron is in the ferrous state. The ability of HasAyp to acquire the ferrous heme iron might be beneficial to Y. pseudotuberculosis, a facultative anaerobe in the Enterobacteriaceae family.
      Graphical abstract image

      PubDate: 2014-05-27T11:29:22Z
       
  • Proton and gallium(III) binding properties of a biologically active
           salicylidene acylhydrazide
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Shoghik Hakobyan , Jean-François Boily , Madeleine Ramstedt
      Bacterial biofilm formation causes a range of problems in our society, especially in health care. Salicylidene acylhydrazides (hydrazones) are promising antivirulence drugs targeting secretion systems used during bacterial infection of host cells. When mixed with the gallium ion they become especially potent as bacterial and biofilm growth-suppressing agents, although the mechanisms through which this occurs are not fully understood. At the base of this uncertainty lies the nature of hydrazone–metal interactions. This study addresses this issue by resolving the equilibrium speciation of hydrazone–gallium aqueous solutions. The protonation constants of the target 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) hydrazone species and of its 2,4,6-trihydroxybenzaldehyde and oxamic acid hydrazide building blocks were determined by UV–visible spectrophotometry to achieve this goal. These studies show that the hydrazone is an excessively strong complexing agent for gallium and that its antivirulence properties are predominantly ascribed to monomeric 1:1Ga–ME0163 complexes of various Ga hydrolysis and ME0163 protonation states. The chelation of Ga(III) to the hydrazone also increased the stability of the compounds against acid-induced hydrolysis, making this group of compounds very interesting for biological applications where the Fe-antagonist action of both Ga(III) and the hydrazone can be combined for enhanced biological effect.
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • Silver(I)/6-hydroxyiminolumazine compounds differently modify
           renin-angiotensin system-regulating aminopeptidases A and N in human
           neuroblastoma and glioma cells
    • Abstract: Publication date: Available online 21 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Mª. Jesús Ramírez-Expósito , Mª. Dolores Mayas-Torres , Mª. Pilar Carrera-González , Sonia B. Jiménez-Pulido , Nuria A. Illán-Cabeza , Purificación Sánchez-Sánchez , Francisco Hueso-Ureña , José M. Martínez-Martos , Miguel N. Moreno-Carretero
      We have described that local tissue renin-angiotensin-system (RAS) is involved in tumor growth in a rat model of experimental glioma in vivo, through the modification of their corresponding local proteolytic regulatory enzymes. Thus, we have found a time-dependent significant decrease in aminopeptidase N (APN) and a significant increase in aminopeptidase A (APA) activities concomitantly with tumor growth in tumor tissue whereas no changes were found in circulating aminopeptidase activities; we suggested that angiotensin peptides may play an essential step in both tumor infiltration and associated angiogenesis. Here we analyze in vitro the antiproliferative efficacy, apoptotic properties and effects of three new disilver complexes containing E-6-(hydroxyimino)ethyl-1,3,7-trimethyllumazine (lumazine=pteridine-2,4(1H,3H)-dione) on RAS-regulating APA and APN specific activities in human neuroblastoma and glioma cell lines NB69 and U373-MG. Disilver compounds showed cytotoxicity against both cell lines, although their potency was different for each cell type. Furthermore, NB69 cells need higher concentrations of silver complexes than U373-MG cells to obtain a 50% growth inhibition. All compounds showed apoptotic effects, being U373-MG cells more susceptible. The three silver complexes tested also show a dose-dependent inhibitory effect on APA activity in NB69 and U373-MG cells, although U373-MG cells are more sensitive. On the contrary, none of them showed effects on APN activity in NB69 neuroblastoma cells whereas the three compounds showed a dose-dependent stimulatory effect on APN activity in U373-MG glioma cells with a similar potency. Disilver complexes show specific antitumor activity against brain tumor cells acting through the paracrine regulating system mediated by local tissue RAS.
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • The gallium(III)–salicylidene acylhydrazide complex shows
           synergistic anti-biofilm effect and inhibits toxin production by
           Pseudomonas aeruginosa
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Olena Rzhepishevska , Shoghik Hakobyan , Barbro Ekstrand-Hammarström , Yvonne Nygren , Torbjörn Karlsson , Anders Bucht , Mikael Elofsson , Jean-François Boily , Madeleine Ramstedt
      Bacterial biofilms cause a range of problems in many areas and especially in health care. Biofilms are difficult to eradicate with traditional antibiotics and consequently there is a need for alternative ways to prevent and/or remove bacterial biofilms. Furthermore, the emergence of antibiotic resistance in bacteria creates a challenge to find new types of antibiotics with a lower evolutionary pressure for resistance development. One route to develop such drugs is to target the so called virulence factors, i.e. bacterial systems used when bacteria infect a host cell. This study investigates synergy effects between Ga(III) ions, previously reported to suppress biofilm formation and growth in bacteria, and salicylidene acylhydrazides (hydrazones) that have been proposed as antivirulence drugs targeting the type three secretion system used by several Gram-negative pathogens, including Pseudomonas aerugionosa, during bacterial infection of host cells. A library of hydrazones was screened for: Fe(III) binding, enhanced anti-biofilm effect with Ga(III) on P. aeruginosa, and low cytotoxicity to mammalian cells. The metal coordination for the most promising ligand, 2-Oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) with Ga(III) was investigated using extended X-ray absorption fine structure spectroscopy as well as density functional theory. The results showed that Ga(III) chelates the hydrazone with 5- and 6-membered chelating rings, and that the Ga(III)–ME0163 complex enhanced the antibiofilm effect of Ga(III) while suppressing the type three secretion system in P. aeruginosa. The latter effect was not observed for the hydrazone alone and was similar for Ga(III)–citrate and Ga(III)–ME0163 complexes, indicating that the inhibition of virulence was caused by Ga(III).
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • Rat liver antioxidant response to iron and copper overloads
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Rosario Musacco-Sebio , Christian Saporito-Magriñá , Jimena Semprine , Horacio Torti , Nidia Ferrarotti , Mauricio Castro-Parodi , Alicia Damiano , Alberto Boveris , Marisa G. Repetto
      The rat liver antioxidant response to Fe and Cu overloads (0–60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58–66%) and Cu (79–81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110–124μgFe/g and 40–50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60–75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30–92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8–8.5h and Mn-SOD: t1/2: 8.5–8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22–39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.
      Graphical abstract image

      PubDate: 2014-05-17T21:27:27Z
       
  • Effect of structure and composition of nickel(II) complexes with
           salicylidene Schiff base ligands on their DNA/protein interaction and
           cytotoxicity
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Peng li , MeiJu Niu , Min Hong , Shuang Cheng , JianMin Dou
      Three new salicylidene Schiff base nickel(II) complexes [Ni(L1)(CH3COOH)2]2 (1), [Ni2(L1)2(CH3OH)] (2), [Ni(L2)2]·3H2O (3) {H2L1 =N,N′-bis(salicylidene)-3,6-dioxa-1,8-diaminooctane, HL2 =2-ethyl-2-(2-hydroxybenzylideneamino)propane-1,3-diol} were synthesized and characterized fully by structural, analytical, and spectral methods. The single-crystal X-ray structures of complexes 1 and 2 exhibit the symmetrical ligands coordinated to the nickel(II) ion in a tetradentate fashion via ONNO donor atoms, while the unsymmetrical ligand L2 presented a ONO tridentate coordination mode in complex 3. The nickel(II) ions lie in the six-coordinated octahedral environment for the mononuclear complexes 1 and 3, along with dinuclear complex 2. The interaction of the complexes with calf thymus DNA (CT-DNA) has been explored by absorption and emission titration methods, which revealed that complexes 1–3 could interact with CT-DNA through intercalation. The interactions of the complexes with bovine serum albumin (BSA) were also investigated using UV–Vis, fluorescence and synchronous fluorescence spectroscopic methods. The results indicated that all of the complexes could quench the intrinsic fluorescence of BSA in a static quenching process. Further, the in vitro cytotoxic effect of the complexes examined on cancerous cell lines such as human lung carcinoma cell line (A549), human colon carcinoma cell lines (HCT-116), human promyelocytic leukemia cells (HL-60) and colonic cancer cell line Caco-2 showed that all three complexes exhibited substantial cytotoxic activity.
      Graphical abstract image

      PubDate: 2014-05-17T21:27:27Z
       
  • Comparative thermal and thermodynamic study of DNA chemically modified
           with antitumor drug cisplatin and its inactive analog transplatin
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Dmitri Y. Lando , Chun-Ling Chang , Alexander S. Fridman , Inessa E. Grigoryan , Elena N. Galyuk , Ya-Wei Hsueh , Chin-Kun Hu
      Antitumor activity of cisplatin is exerted by covalent binding to DNA. For comparison, studies of cisplatin-DNA complexes often employ the very similar but inactive transplatin. In this work, thermal and thermodynamic properties of DNA complexes with these compounds were studied using differential scanning calorimetry (DSC) and computer modeling. DSC demonstrates that cisplatin decreases thermal stability (melting temperature, Tm ) of long DNA, and transplatin increases it. At the same time, both compounds decrease the enthalpy and entropy of the helix–coil transition, and the impact of transplatin is much higher. From Pt/nucleotide molar ratio rb =0.001, both compounds destroy the fine structure of DSC profile and increase the temperature melting range (ΔT). For cisplatin and transplatin, the dependences δTm vs rb differ in sign, while δΔT vs rb are positive for both compounds. The change in the parameter δΔT vs rb demonstrates the GC specificity in the location of DNA distortions. Our experimental results and calculations show that 1) in contrast to [Pt(dien)Cl]Cl, monofunctional adducts formed by transplatin decrease the thermal stability of long DNA at [Na+]>30mM; 2) interstrand crosslinks of cisplatin and transplatin only slightly increase Tm ; 3) the difference in thermal stability of DNA complexes with cisplatin vs DNA complexes with transplatin mainly arises from the different thermodynamic properties of their intrastrand crosslinks. This type of crosslink appears to be responsible for the antitumor activity of cisplatin. At any [Na+] from interval 10–210mM, cisplatin and transplatin intrastrand crosslinks give rise to destabilization and stabilization, respectively.
      Graphical abstract image

      PubDate: 2014-05-13T21:28:44Z
       
  • Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a]
           pyrimidin-7(4h)-one and their therapeutic potential to fight leishmaniasis
           and Chagas disease
    • Abstract: Publication date: Available online 6 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Ana B. Caballero , Antonio Rodríguez-Diéguez , Juan M. Salas , Manuel Sánchez-Moreno , Clotilde Marín , Inmaculada Ramírez-Macías , Noelia Santamaría-Díaz , Ramón Gutierrez-Sánchez
      In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons, have led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III), Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease.
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      PubDate: 2014-05-09T21:28:27Z
       
  • New bioactive 2,6-diacetylpyridine bis(p-chlorophenylthiosemicarbazone)
           ligand and its Pd(II) and Pt(II) complexes: Synthesis, characterization,
           cytotoxic activity and DNA binding ability
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Ana I. Matesanz , Carolina Hernández , Pilar Souza
      Preparation and characterization of 2,6-diacetylpyridine bis(4 N-p-chlorophenylthiosemicarbazone) ligand, H2L, and its palladium(II) and platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of the two new complexes has been determined by single crystal X-ray diffraction. The ligand act as dianionic tetradentate donor coordinating to the metal center in a square planar geometry through the pyridine nitrogen atom and the azomethine nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the hydrazine nitrogen atom of the other arm. New free ligand and its metal complexes have been evaluated for antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H2L and [PtL] since they are capable of not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in breast cancer T-47D cells. The interaction of H2L with calf thymus DNA was also investigated and its binding constant (Kb) determined.
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      PubDate: 2014-05-09T21:28:27Z
       
  • Complexing ability of (-)-cytisine – synthesis, spectroscopy and
           crystal structures of the new copper and zinc complexes
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Anna K. Przybył , Maciej Kubicki , Renata Jastrząb
      For the first time the NMR spectra of quinolizidine alkaloid with Cu(II) are studied. Structures of new complexes of (-)-cytisine with Cu+2 and Zn+2 cations are visualized, discussed in detail and characterized by spectroscopic methods: ESI-MS, NMR, UV-vis, EPR and crystallographic methods. In solution metal coordinates through the protonated nitrogen atoms of secondary amino groups (in piperidine ring) of cytisine molecule. While in solid state the most stable structures of the complexes are those in which the coordination of Cu(II) and Zn(II) salts is realized solely through the lactam carbonyl oxygen atom.
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      PubDate: 2014-05-09T21:28:27Z
       
  • Tyrosine nitration in peptides by peroxynitrite generated in situ in a
           light-controlled platform: Effects of pH and thiols
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Tara R. deBoer , Rafael I. Palomino , Sharon O. Idiga , Glenn L. Millhauser , Pradip K. Mascharak
      Peroxynitrite has been shown to play a critical role in inflammation and affords 3-nitrotyrosine as the hallmark product. The reported methods of generating this reactive nitrogen species in situ often fails to provide a high and steady flux of peroxynitrite resulting in poor yields of 3-nitrotyrosine. Herein we report a two-component peroxynitrite-generating platform in which this anion is produced in a biomimetic fashion and under the control of visible light. Incorporation of the nitric oxide- and superoxide-generating components in polymer matrices allows easy alterations of pH in the reaction wells of this platform. We have demonstrated very efficient nitration of tyrosine by peroxynitrite at different pH values and with varying concentrations of carbonate. In addition to tyrosine, a set of tyrosine-containing peptides was also studied. Presence of glutathione in the reaction wells increases the extent of tyrosine nitration in such peptide substrates presumably by raising the lifetime of nitric oxide in the reaction medium. When a cysteine residue was included in the sequence of the peptide, the extent of nitration of the tyrosine residue was found to depend on the position of the cysteine residue with respect to tyrosine. The extent of tyrosine nitration is strongly attenuated when the cysteine residue is directly adjacent to the tyrosine. This effect has been attributed to an intramolecular radical transfer mechanism. Taken together, results of this study demonstrate the potential of this light-controlled platform as a convenient bioanalytical tool in studying the reactions of peroxynitrite under widely varying conditions.
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      PubDate: 2014-05-09T21:28:27Z
       
  • Spin equilibrium and O2-binding kinetics of Mycobacterium tuberculosis
           CYP51 with mutations in the histidine–threonine dyad
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Gareth K. Jennings , Anuja Modi , Justin E. Elenewski , Caroline M. Ritchie , Thuy Nguyen , Keith C. Ellis , John C Hackett
      The acidic residues of the “acid–alcohol pair” in CYP51 enzymes are uniformly replaced with histidine. Herein, we adopt the Mycobacterium tuberculosis (mt) enzyme as a model system to investigate these residues' roles in finely tuning the heme conformation, iron spin state, and formation and decay of the oxyferrous enzyme. Properties of the mtCYP51 and the T260A, T260V, and H259A mutants were interrogated using UV–Vis and resonance Raman spectroscopies. Evidence supports that these mutations induce comprehensive changes in the heme environment. The heme iron spin states are differentially sensitive to the binding of the substrate, dihydrolanosterol (DHL). DHL and clotrimazole perturb the local environments of the heme vinyl and propionate substituents. Molecular dynamics (MD) simulations of the DHL–enzyme complexes support that the observed perturbations are attributable to changes in the DHL binding mode. Furthermore, the rates of the oxyferrous formation were measured using stopped-flow methods. These studies demonstrate that both HT mutations and DHL modulate the rates of oxyferrous formation. Paradoxically, the binding rate to the H259A mutant–DHL complex was approximately four-fold that of mtCYP51, a phenomenon that is predicted to result from the creation of an additional diffusion channel from loss of the H259–E173 ion pair in the mutant. Oxyferrous enzyme auto-oxidation rates were relatively constant, with the exception of the T260V-DHL complex. MD simulations lead us to speculate that this behavior may be attributed to the distortion of the heme macrocycle by the substrate.
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      PubDate: 2014-05-09T21:28:27Z
       
  • Cu(II)-catalyzed oxidation of dopamine in aqueous solutions: Mechanism and
           kinetics
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): A. Ninh Pham , T. David Waite
      Spontaneous oxidation of dopamine (DA) and the resultant formation of free radical species within dopamine neurons of the substantia nigra (SN) is thought to bestow a considerable oxidative load upon these neurons and may contribute to their vulnerability to degeneration in Parkinson's disease (PD). An understanding of DA oxidation under physiological conditions is thus critical to understanding the relatively selective vulnerability of these dopaminergic neurons in PD and may support the development of novel neuro-protective approaches for this disorder. In this study, the oxidation of dopamine (0.2–10μM) was investigated both in the absence and the presence of copper (0.01–0.4μM), a redox active metal that is present at considerable concentrations in the SN, over a range of background chloride concentrations (0.01–0.7M), different oxygen concentrations and at physiological pH7.4. DA was observed to oxidize extremely slowly in the absence of copper and at moderate rates only in the presence of copper but without chloride. The oxidation of DA however was significantly enhanced in the presence of both copper and chloride with the rate of DA oxidation greatest at intermediate chloride concentrations (0.05–0.2M). The variability of the catalytic effect of Cu(II) on DA oxidation at different chloride concentrations can be explained and successfully modeled by appropriate consideration of the reaction of Cu(II) species with DA and the conversion of Cu(I) to Cu(II) through oxygenation. This model suggests that the speciation of Cu(II) and Cu(I) is critically important to the kinetics of DA oxidation and thus the vulnerability to degradation of dopaminergic neuron in the brain milieu.
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      PubDate: 2014-05-09T21:28:27Z
       
  • Metal ions modulate thermal aggregation of beta-lactoglobulin: A joint
           chemical and physical characterization
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Giovanna Navarra , Anna Tinti , Michele Di Foggia , Maurizio Leone , Valeria Militello , Armida Torreggiani
      Molecular basis of the role played by Cu2+ and Zn2+ ions during the thermal aggregation processes of beta-lactoglobulin (BLG) was studied by using a joint application of different techniques. In particular, Raman spectroscopy was very useful in identifying the different effects caused by the two metals at molecular level (i.e. changes in His protonation state, disulfides bridge conformation, and micro-environment of aromatic residues), evidencing the primary importance of the protein charge distribution during the aggregation process. Both metal ions are able to act on this factor and favor the protein aggregation, but Zn2+ is able to alter the natural conformational state of BLG, causing a slight unfolding, whereas Cu2+ ions play a role only during the thermal treatment. Thus, Zn2+ ions favor the formation of bigger aggregates and branched fibril-like structures, whereas for Cu2+ ions a greater number of cross-beta structures during thermal incubation and finally, fibrillar structures. The aggregation process occurs in two phases, as suggested by the measurements on the time evolution of the BLG aggregates: the first one is characterized by a partial unfolding of the protein and aggregate growth, forming oligomers and protofibrils, whereas the second one is characterized by further supramolecular assembly, leading to the formation of fibrils.
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      PubDate: 2014-05-09T21:28:27Z
       
  • The type 1 copper site of pseudoazurin: Axial and rhombic
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Peter Gast , Freek G.J. Broeren , Silvia Sottini , Risa Aoki , Akiko Takashina , Takahide Yamaguchi , Takamitsu Kohzuma , Edgar J.J. Groenen
      We report on a high-frequency electron-paramagnetic-resonance study of the type 1 copper site of pseudoazurin. The spectra fully resolve the contribution of a nearly axial spectrum besides the rhombic spectrum, which unequivocally proves the existence of two conformations of the copper site. Pseudoazurins have been considered from Achromobacter cycloclastes including eight mutants and from Alcaligenes faecalis. The two conformations are virtually the same for all pseudoazurins, but the rhombic/axial population varies largely, between 91/9 and 33/67. These observations are discussed in relation to optical absorption spectra and X-ray diffraction structures. A similar observation for fern plastocyanin from Dryopteris crassirhizoma suggests that dual conformations of type 1 copper sites are more common.
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      PubDate: 2014-05-09T21:28:27Z
       
  • The cytotoxicity of the anticancer drug elesclomol is due to oxidative
           stress indirectly mediated through its complex with Cu(II)
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Brian B. Hasinoff , Arun A. Yadav , Daywin Patel , Xing Wu
      Elesclomol is an anticancer drug that is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with Cu(II) and may exert its anticancer activity through the induction of oxidative stress and/or its ability to transport copper into the cell. A UV–vis spectrophotometric titration showed that Cu(I) also formed a 1:1 complex with elesclomol. Ascorbic acid, but not glutathione or NADH, potently reduced the Cu(II)-elesclomol complex to produce hydrogen peroxide. Even though hydrogen peroxide mediated reoxidation of the copper(I) produced by ascorbic acid reduction has the potential to lead to hydroxyl radical formation, electron paramagnetic resonance spin trapping experiments, either with or without added hydrogen peroxide, showed that the ascorbic acid-reduced Cu(II)-elesclomol complex could not directly generate damaging hydroxyl radicals. Both Cu(II)-elesclomol and elesclomol potently oxidized dichlorofluorescin in K562 cells. The highly specific copper chelators tetrathiomolybdate and triethylenetetramine were found to greatly reduce the cytotoxicity of both elesclomol and Cu(II)-elesclomol complex towards erythroleukemic K562 cells, consistent with a role for copper in the cytotoxicity of elesclomol. The superoxide dismutating activity of Cu(II)-elesclomol was much lower than that of Cu(II). Depletion of glutathione levels in K562 cells by treatment with buthionine sulfoximine sensitized cells to both elesclomol and Cu(II)-elesclomol. In conclusion, these results showed that elesclomol indirectly inhibited cancer cell growth through Cu(II)-mediated oxidative stress.
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      PubDate: 2014-05-05T06:17:40Z
       
  • Two water-soluble copper(II) complexes: Synthesis, characterization, DNA
           cleavage, protein binding activities and in vitro anticancer activity
           studies
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Jing Lu , Qian Sun , Jun-Ling Li , Lin Jiang , Wen Gu , Xin Liu , Jin-Lei Tian , Shi-Ping Yan
      Two water-soluble ternary copper(II) complexes of [Cu(L)Cl](ClO4) (1) and [Cu(L)Br2] (2) (L =(2-((quinolin-8-ylimino)methyl)pyridine)) were prepared and characterized by various physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square-pyramidal CuN3Cl2 (1) or CuN3Br2 (2) geometry in which Schiff-base L acts as a neutral tridentate ligand. Both complexes present intermolecular π–π stacking interactions between quinoline and pyridine rings. The interaction of two complexes with CT-DNA (calf thymus-DNA) and BSA (bovine serum albumin) was studied by means of various spectroscopy methods, which revealed that 1 and 2 could interact with CT-DNA through intercalation mode, and could quench the intrinsic fluorescence of BSA in a static quenching process. Furthermore, the competition experiment using Hoechst 33258 indicated that two complexes may bind to CT-DNA by a minor groove. DNA cleavage experiments indicate that the complexes exhibit efficient DNA cleavage activities without any external agents, and hydroxyl radical (HO) and singlet oxygen (1O2) may serve as the major cleavage active species. Notably, the in vitro cytotoxicity of the complexes on three human tumor cells lines (HeLa, MCF-7, and A549) demonstrates that two compounds have broad-spectrum antitumor activity with quite low IC50 ranges of 0.43–1.85μM. Based on the cell cycle experiments, 1 and 2 could delay or inhibit cell cycle progression through the S phase.
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      PubDate: 2014-05-05T06:17:40Z
       
  • Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded
           water-soluble amino acid-modified β-cyclodextrin platinum complexes
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Mei-Xia Zhao , Meng Zhao , Er-Zao Zeng , Yang Li , Jin-Ming Li , Qian Cao , Cai-Ping Tan , Liang-Nian Ji , Zong-Wan Mao
      The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV–visible (UV–vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug.
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      PubDate: 2014-05-05T06:17:40Z
       
  • A platinum(II) complex of liriodenine from traditional Chinese medicine
           (TCM): Cell cycle arrest, cell apoptosis induction and telomerase
           inhibition activity via G-quadruplex DNA stabilization
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Yu-Lan Li , Qi-Pin Qin , Yan-Cheng Liu , Zhen-Feng Chen , Hong Liang
      Liriodenine (L), an antitumor active ingredient from the traditional Chinese medicine (TCM), Zanthoxylum nitidum, afforded a platinum(II) complex (1) of L, cis-[PtCl2(L)(DMSO)], which previously reported for its in vitro antitumor activity and intercalative binding with DNA. In this study, complex 1 was further discussed for its antitumor mechanism and structure–activity relationship, comparing with L and cisplatin. Towards the most sensitive BEL-7404 human hepatoma cells, complex 1 significantly induced cell cycle arrest at both G2/M phase and S phase. It suggests that double helix DNA is not the simplex intracellular target for 1. On the other hand, the BEL-7404 cells incubated with 1 and stained by Hoechst 33258 and AO/EB showed typical cell apoptosis in dose-dependent manner. The BEL-7404 cells incubated with 1 and stained by JC-1 were also characteristic for cell apoptosis on the loss of mitochondrial membrane potential. Furthermore, the G-quadruplex DNA binding property of complex 1 was also investigated by spectroscopic analyses, fluorescent indicator displacement (FID) assay and fluorescence resonance energy transfer (FRET) assay. The results indicated that 1 stabilized the human telomeric G4-HTG21 DNA better than L. The telomerase inhibition ratio of 1 ((62.50±0.03)%), which was examined by telomerase polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), was much higher than L ((21.77±0.01)%). It can be ascribed to the better G4-HTG21 DNA stabilization of 1 than L. The results suggested that the nuclei, mitochondria and telomerase via G-quadruplex DNA stabilization all should be key targets for the antitumor mechanism of 1, in which the central platinum(II) played a key role.
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      PubDate: 2014-05-05T06:17:40Z
       
  • Synthesis, characterization, crystal structures and biological activity of
           set of Cu(II) benzothiazole complexes: Artificial nucleases with cytotoxic
           activities
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Ramsey A. Steiner , David Foreman , Han X. Lin , Bruce K. Carney , Kristin M. Fox , Lynne Cassimeris , Joseph M. Tanski , Laurie A. Tyler
      A series of Cu(II) complexes with ligand frames based on quinoline derivatives appended with a benzothiazole substituent has been isolated. The complexes, Cu(Q(oBt))(NO3)2(H2O)∙CH3OH (1 ∙CH3OH), Cu(8OHQ(oBt))Cl2 ∙CH3OH (2 ∙CH3OH), Cu(8OQ(oBt))Cl(CH3OH)∙CH3OH (3 ∙CH3OH) and [Cu(8OH1/2Q(oBt))(CH3OH)(NO3)]2(NO3) (4) have been characterized by single crystal X-ray diffraction, IR and UV-visible spectroscopies, and elemental analysis. The ligand frame within the set of complexes differs in the substituent on the quinoline ring: complex 1 remains unsubstituted at this position while complexes 2–4 have a substituted OH group. In complex 2, the bound phenol remains protonated while in 3 it is a phenolato group. Complex 4 contains two complexes within the unit cell and one NO3 − giving rise to an overall ‘half-protonation’. The interaction between complexes 1–3 with CT-DNA was investigated using fluorescence emission spectroscopy and revealed 2 and 3 strongly intercalate DNA with Kapp values of 1.47×107 M−1 and 3.09×107 M−1, respectively. The ability of complexes 1–3 to cleave SC-DNA was monitored using gel electrophoresis. Each complex exhibits potent, concentration dependent nuclease activity forming single and double-nicked DNA as low as 10μM. The nuclease activity of complexes 1–3 is primarily dependent on 1O2 species while ·OH radicals play a secondary role in the cleavage by complexes 2 and 3. The cytotoxic effects of 1–3 were examined using HeLa cells and show cell death in the micromolar range. The distribution of cell cycle stages remains unchanged when complexes are present indicating DNA damage may be occurring throughout the cell cycle.
      Graphical abstract image

      PubDate: 2014-05-05T06:17:40Z
       
  • Inductively coupled plasma mass spectrometry for metallodrug development:
           Albumin binding and serum distribution of cytotoxic cis- and
           trans-isomeric platinum(II) complexes
    • Abstract: Publication date: Available online 22 April 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Konstantin Ossipov , Yulia Y. Scaffidi-Domianello , Irina F. Seregina , Markus Galanski , Bernhard K. Keppler , Andrei R. Timerbaev , Mikhail A. Bolshov
      Binding to plasma proteins is one of the major metabolic pathways of metallodrugs. In the case of platinum-based anticancer drugs, it is interaction with serum albumin that affects most strongly their in vivo behavior. Since both the configuration, i.e. cis-trans-isomerism, and the nature of leaving groups have an effect on the reactivity of Pt(II) coordination compounds toward biomolecules, a set of cis- and trans-configured complexes with halide leaving groups (Cl–, Br–, and I–) and 2-propanone oxime as carrier ligands was chosen for this study. Binding experiments were performed both with albumin and human serum and the Pt content in ultrafiltrates was quantified using inductively coupled plasma mass spectrometry. In order to shed light on the binding mechanism, the albumin binding constant (K HSA) and the octanol–water partition coefficient (P) were experimentally determined and relationships between log K HSA and log P were explored. The correlation was found significant only for cis-configured platinum complexes (R 2 =0.997 and standard deviation=0.02), indicating a certain contribution of the nonspecific binding which is largely dominated by the lipophilicity of compounds. In contrast, for trans-complexes a specific molecular recognition element plays a significant role. The participation of albumin in drug distribution in blood serum was assessed using an equilibrium distribution model and by comparing the percentage binding in the albumin and serum-protein fractions. Irrespective of the compound polarity, albumin contributes from 85 to 100% to the overall binding in serum.
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      PubDate: 2014-04-26T06:16:12Z
       
  • Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and
           antioxidant status in the liver of STZ-induced diabetic rats
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Mingxia Xie , Deliang Chen , Fang Zhang , Gail R. Willsky , Debbie C. Crans , Wenjun Ding
      Vanadium compounds exert various insulin-mimetic and anti-diabetic effects both in vitro and in vivo. Vanadium(III, IV, V)-chlorodipicolinate (Vdipic-Cl) compounds, including H[VIII(dipic-Cl)2]·5H2O (V3dipic-Cl), VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[VVO2(dipic-Cl)] (V5dipic-Cl), were synthesized with the indicated oxidation states. The present study was conducted to investigate if chemical valence and anti-oxidation effects of vanadium compounds are involved in the anti-diabetic effects observed in streptozotocin (STZ)-induced diabetic rats treated with these vanadium compounds. V3dipic-Cl, V4dipic-Cl, V5dipic-Cl, inorganic vanadium salts vanadyl sulfate (VOSO4) or sodium metavanadate (NaVO3) were orally administered in drinking water (50μgV/ml) to STZ-induced diabetic rats for 28days. The results showed that Vdipic-Cl treatment significantly improved hyperglycemia and glucose intolerance, as well as increased hepatic glycogen synthesis in diabetic rats. The mRNA levels of key glycolytic enzymes in liver, phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GK), and L-pyruvate kinase (L-PK) altered in diabetic animals were significantly restored towards normal values by treatment with some of the vanadium compounds. Moreover, the diabetes elevated activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in serum were significantly decreased after treatment with Vdipic-Cl complexes. Furthermore, treatment of diabetic rats with V4dipic-Cl and V5dipic-Cl compounds significantly reduced malondialdehyde (MDA) production and increased glutathione peroxidase (GSH-Px) and catalase (CAT) activities. These data suggest that vanadium compounds with the indicated chemical valence promote glycogen synthesis and recover suppressed glycolysis in the liver of diabetic rats due to their capacity to reduce oxidative stress by stimulating antioxidant enzymes.
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      PubDate: 2014-04-21T21:26:32Z
       
  • Selective hydrolysis of hen egg white lysozyme at Asp-X peptide bonds
           promoted by oxomolybdate
    • Abstract: Publication date: Available online 12 April 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Karen Stroobants , Phuong Hien Ho , Eva Moelants , Paul Proost , Tatjana N. Parac-Vogt
      The activity of oxomolybdate(VI) towards hen egg white lysozyme (HEWL) was examined under physiological and slightly acidic pH conditions. Purely hydrolytic cleavage of HEWL in the presence of 10 to 100mM of oxomolybdate(VI) after incubation at pH5.0 and 60°C for 2 to 7days was observed in SDS-PAGE experiments. Four cleavage sites, which all occurred at Asp-X sequences and included the Asp18-Asn19, Asp48-Gly49, Asp52-Trp53 and Asp101-Gly102 peptide bonds, were identified with Edman degradation. The molecular interaction between [MoO4]2- and HEWL was studied by circular dichroism (CD) and 1H-15 N heteronuclear single quantum correlation (HSQC) NMR spectroscopy. CD spectroscopy revealed a significant decrease in the α-helical content of HEWL upon addition of oxomolybdate, while 1H-15 N HSQC NMR spectroscopy identified the residues which were most affected upon interaction with [MoO4]2-. 95Mo NMR measurements, performed on oxomolybdate solutions containing HEWL, identified the monomeric [MoO4]2- form as active species in the hydrolytic reaction. The hydrolysis of the Asp-Gly model peptide in the presence of oxomolybdate(VI) was studied by 1H NMR, further supporting a hydrolytic mechanism where polarization of the carbonyl is followed by internal nucleophilic attack on the Asp residue.
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      PubDate: 2014-04-17T06:26:01Z
       
  • Editorial Board
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135




      PubDate: 2014-04-17T06:26:01Z
       
  • Contents
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135




      PubDate: 2014-04-17T06:26:01Z
       
  • Dilution of dipolar interactions in a spin-labeled, multimeric
           metalloenzyme for DEER studies
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Mahesh Aitha , Timothy K. Richmond , Zhenxin Hu , Alyssa Hetrick , Raquel Reese , Althea Gunther , Robert McCarrick , Brian Bennett , Michael W. Crowder
      The metallo-β-lactamases (MβLs), which require one or two Zn(II) ions in their active sites for activity, hydrolyze the amide bond in β-lactam-containing antibiotics, and render the antibiotics inactive. All known MβLs contain a mobile element near their active sites, and these mobile elements have been implicated in the catalytic mechanisms of these enzymes. However little is known about the dynamics of these elements. In this study, we prepared a site-specific, double spin-labeled analog of homotetrameric MβL L1 with spin labels at positions 163 and 286 and analyzed the sample with DEER (double electron electron resonance) spectroscopy. Four unique distances were observed in the DEER distance distribution, and these distances were assigned to the desired intramolecular dipolar coupling (between spin labels at positions 163 and 286 in one subunit) and to intermolecular dipolar couplings. To rid the spin-labeled analog of L1 of the intermolecular couplings, spin-labeled L1 was “diluted” by unfolding/refolding the spin-labeled enzyme in the presence of excess wild-type L1. DEER spectra of the resulting, spin-diluted enzyme revealed a single distance corresponding to the desire intramolecular dipolar coupling.
      Graphical abstract image

      PubDate: 2014-04-17T06:26:01Z
       
  • Anion inhibition studies of two α-carbonic anhydrases from Lotus
           japonicus, LjCAA1 and LjCAA2
    • Abstract: Publication date: Available online 8 April 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Daniela Vullo , Emmanouil Flemetakis , Andrea Scozzafava , Clemente Capasso , Claudiu T. Supuran
      The model organism for the investigation of symbiotic nitrogen fixation in legumes Lotus japonicus encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-class, LjCAA1 and LjCAA2. Here we report the kinetic characterization and inhibition of these two CAs with inorganic and complex anions and other molecules interacting with zinc proteins, such as sulfamide, sulfamic acid, phenylboronic/arsonic acids. LjCAA1 showed a high catalytic activity for the CO2 hydration reaction, with a kcat of 7.4*105 s−1 and a kcat/Km of 9.6*107 M−1 s−1 and was inhibited in the low micromolar range by N,N-diethyldithiocarbamate, sulfamide, sulfamic acid, phenylboronic/arsonic acid (KIs of 4 – 62 μM). LjCAA2 showed a moderate catalytic activity for the physiologic reaction, with a kcat of 4.0*105 s−1 and a kcat/Km of 4.9*107 M−1 s−1. The same anions mentioned above for the inhibition of LjCAA1 showed the best activity against LjCAA2 (KIs of 7 – 29 μM). Nitrate and nitrite, anions involved in nitrogen fixation showed lower affinity for the two enzymes, with inhibition constants in the range of 3.7 – 7.0mM. Halides and sulfate also behaved in a distinct manner towards the two enzymes investigated here. As LjCAA1/2 participate in the pH regulation processes and CO2 metabolism within the nitrogen-fixing nodules of the plant, our studies may shed some light regarding these complex biochemical processes.
      Graphical abstract image

      PubDate: 2014-04-12T11:13:37Z
       
  • Antiparasitic activities of novel ruthenium/lapachol complexes
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Marília I.F. Barbosa , Rodrigo S. Corrêa , Katia Mara de Oliveira , Claudia Rodrigues , Javier Ellena , Otaciro R. Nascimento , Vinícius P.C. Rocha , Fabiana R. Nonato , Taís S. Macedo , José Maria Barbosa-Filho , Milena B.P. Soares , Alzir A. Batista
      The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4′-methylbipyridine (Me-bipy) and 4,4′-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6 (3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3 =triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV–vis spectroscopy, 31P{1H} and 1H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol–ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.
      Graphical abstract image

      PubDate: 2014-04-12T11:13:37Z
       
  • Direct thermodynamic and kinetic measurements of Fe2+ and Zn2+ binding to
           human serum transferrin
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Tyson Terpstra , Justin McNally , Thi-Hong-Lien Han , Nguyet-Thanh Ha-Duong , Jean-Michel El-Hage-Chahine , Fadi Bou-Abdallah
      Human serum transferrin (hTf) is a single-chain bilobal glycoprotein that efficiently delivers iron to mammalian cells by endocytosis via the transferrin/transferrin receptor system. While extensive studies have been directed towards the study of ferric ion binding to hTf, ferrous ion interactions with the protein have never been firmly investigated owing to the rapid oxidation of FeII to FeIII and the difficulty in maintaining a fully anaerobic environment. Here, the binding of Fe2+ and Zn2+ ions to hTf has been studied under anaerobic and aerobic conditions, respectively, in the presence and absence of bicarbonate by means of isothermal titration calorimetry (ITC) and fluorescence spectroscopy. The ITC data indicate the presence of one class of strong binding sites with dissociation constants of 25.2nM for Fe2+ and 6.7nM for Zn2+ and maximum binding stoichiometries of 1 Zn2+ (or 1 Fe2+) per hTf molecule. With either metal, the binding interaction was achieved by both favorable enthalpy and entropy changes (ΔH0 approximately −12kJ/mol and ΔS0 ~106J/mol·K for Fe2+ and ΔH0 approximately −18kJ/mol and ΔS0 ~97J/mol·K for Zn2+). The large and positive entropy values are most likely due to the change in the hydration of the protein and the metal ions upon interaction. Rapid kinetics stopped-flow fluorescence spectroscopy revealed two different complexation mechanisms with different degrees of conformational changes upon metal ion binding. Our results are discussed in terms of a plausible scenario for iron dissociation from transferrin by which the highly stable Fe3+–hTf complex might be reduced to the more labile Fe2+ ion before iron is released to the cytosol.
      Graphical abstract image

      PubDate: 2014-04-07T11:23:50Z
       
  • Effects of Mn-doping on the structure and biological properties of
           β-tricalcium phosphate
    • Abstract: Publication date: Available online 3 April 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): P.M.C. Torres , S.I. Vieira , A.R. Cerqueira , S. Pina , O.A.B. da Cruz Silva , J.C.C. Abrantes , J.M.F. Ferreira
      Doping calcium phosphates with trace elements that exist in bone tissues is beneficial in terms of cell-material interactions and in vivo performance of the bone grafts made thereof. Manganese (Mn) is an essential element for normal growth and metabolism of bone tissues, but studies reporting the effects of Mn-doping calcium phosphates are scarce. The present study investigated the influence of Mn-doping on the structure, morphology and biological properties of β-tricalcium phosphate [β-Ca3(PO4)2] (β-TCP). Mn-doped (MnTCP) powders, with Mn contents varying from 0–10mol. %), were obtained through an aqueous precipitation method followed by heat treatment at 800ºC. The successful incorporation of Mn into β-TCP structure was proved through quantitative X-ray diffraction (XRD) phase analysis coupled with structural Rietveld refinement. Increasing Mn concentrations led to decreasing trends of a- and c-axis lattice parameters, and Mn-doping also significantly affected the morphology of β-TCP powders. In vitro proliferation and differentiation assays of MC3T3-E1 osteoblastic-like cells, grown in the presence of the powders, revealed that the biological benefits of Mn-doped β-TCP are limited to lower Mn incorporation levels and potentially related to their surface microstructure. The Mn1-βTCP composition revealed the best set of bioactivity properties, potentially a good candidate for future applications of β-TCP materials in osteoregeneration.
      Graphical abstract image

      PubDate: 2014-04-07T11:23:50Z
       
  • Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer
           agents: Syntheses, crystal structure, DNA cleavage, cytotoxicity and
           apoptosis induction activity
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Jia Shao , Zhong-Ying Ma , Ang Li , Ya-Hong Liu , Cheng-Zhi Xie , Zhao-Yan Qiang , Jing-Yuan Xu
      Four novel thiosemicarbazone metal complexes, [Cu(Am4M)(OAc)]·H2O (1), [Zn(HAm4M)Cl2] (2), [Zn2(Am4M)2Br2] (3) and [Zn2(Am4M)2(OAc)2]·2MeOH (4) [HAm4M=(Z)-2-(amino(pyridin-2-yl)methylene)-N-methylhydrazinecarbothioamide], have been synthesized and characterized by X-ray crystallography, elemental analysis, ESI-MS and IR. X-ray analysis revealed that complexes 1 and 2 are mononuclear, which possess residual coordination sites for Cu(II) ion in 1 and good leaving groups (Cl−) for Zn(II) ion in 2. Both 3 and 4 displayed dinuclear units, in which the metal atoms are doubly bridged by S atoms of two Am4M− ligands in 3 and by two acetate ions in bi- and mono-dentate forms, respectively, in 4. Their antiproliferative activities on human epithelial cervical cancer cell line (HeLa), human liver hepatocellular carcinoma cell line (HepG-2) and human gastric cancer cell line (SGC-7901) were screened. Inspiringly, IC50 value (11.2±0.9μM) of complex 1 against HepG-2 cells was nearly 0.5 fold of that against human hepatic cell lines LO2, showing a lower toxicity to human liver cells. Additionally, it displayed a stronger inhibition on the viability of HepG-2 cells than cisplatin (IC50 =25±3.1μM), suggesting complex 1 might be a potential high efficient antitumor agent. Furthermore, fluorescence microscopic observation and flow cytometric analysis revealed that complex 1 could significantly suppress HepG-2 cell viability and induce apoptosis. Several indexes, such as DNA cleavage, reactive oxygen species (ROS) generation, comet assay and cell cycle analysis indicated that the antitumor mechanism of complex 1 on HepG-2 cells might be via ROS-triggered apoptosis pathway.
      Graphical abstract image

      PubDate: 2014-04-02T21:25:51Z
       
  • Influence of PPh3 moiety in the anticancer activity of new organometallic
           ruthenium complexes
    • Abstract: Publication date: July 2014
      Source:Journal of Inorganic Biochemistry, Volume 136
      Author(s): Rubén Sáez , Julia Lorenzo , Ma Jose Prieto , Mercè Font-Bardia , Teresa Calvet , Nuria Omeñaca , Marta Vilaseca , Virtudes Moreno
      The effect of the PPh3 group in the antitumor activity of some new organometallic ruthenium(II) complexes has been investigated. Several complexes of the type [Ru(II)(Cl)(PPh3)(Lig-N)], [Ru(II)(Cl)2(Lig-N)] (where Lig-N=pyridine derivate) and [Ru(II)(Cl)(PPh3)2], have been synthesized and characterized. A noticeable increment of the antitumor activity and cytotoxicity of the complexes due to the presence of PPh3 moiety has also been demonstrated, affording IC50 values of 5.2μM in HL-60 tumor cell lines. Atomic force microscopy, circular dichroism and electrophoresis experiments have proved that these complexes can bind DNA resulting in a distortion of both secondary and tertiary structures. Ethidium bromide displacement fluorescence spectroscopy studies and viscosity measurements support that the presence of PPh3 group induces intercalation interactions with DNA. Indeed, crystallographic analysis, suggest that intra-molecular π–π interactions could be involved in the intercalation within DNA base pairs. Furthermore, high performance liquid chromatography mass spectrometry (HPLC–MS) studies have confirmed a strong interaction between ruthenium complexes and proteins (ubiquitin and potato carboxypeptidase inhibitor — PCI) including slower kinetics due to the presence of PPh3 moiety, which could have an important role in detoxification mechanism and others. Finally, ion mobility mass spectrometry (IMMS) experiments have proved that there is no significant change in the gas phase structural conformation of the proteins owing to their bonding to ruthenium complexes.
      Graphical abstract image

      PubDate: 2014-03-29T22:15:17Z
       
  • Apo-neocarzinostatin: A protein carrier for Cu(II) glycocomplexes and
           Cu(II) into U937 and HT29 cell lines
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135
      Author(s): Ludivine Garcia , Susanna Franzoni , Francesca Mussi , Magali Aumont-Niçaise , Hélène Bertrand , Michel Desmadril , Giorgio Pelosi , Annamaria Buschini , Clotilde Policar
      In the field of pharmaceuticals there is an increasing need for new delivery systems to overcome the issues of solubility, penetration, toxicity and drug resistance. One of the possible strategies is to use biocarriers such as proteins to encourage the cell-penetration of drugs. In this paper, the use of the apo-protein neocarzinostatin (apo-NCS) as a carrier-protein for two Cu(II) glycocomplexes, previously characterized, and Cu(II) ions was investigated. Its interaction with the metallic compounds was analyzed using microcalorimetry. The dissociation constants were shown to be in the micromolar range. The Cu(II) glycocomplexes, in absence of apo-NCS, were found to be cytotoxic in the U937 and HT29 cell lines whereas the corresponding glycoligands showed no toxicity. The leukemic cell line (U937) seems to be more sensitive to glycocomplexes than the colon cancer cell line (HT29). Interestingly, apo-NCS was shown to increase systematically the antiproliferative activity by a factor of 2 and 3 for Cu(II) glycocomplexes and Cu(II) respectively. The antiproliferative activity detected was not related to proteasome inhibition. This result stresses the importance of new molecular tools for the delivery of Cu(II) to tumor cells using non-covalent association with carriers proteins.
      Graphical abstract image

      PubDate: 2014-03-21T21:46:05Z
       
  • Biological evaluation of bismuth non-steroidal anti-inflammatory drugs
           (BiNSAIDs): Stability, toxicity and uptake in HCT-8 colon cancer cells
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135
      Author(s): Emma L. Hawksworth , Philip C. Andrews , Wilford Lie , Barry Lai , Carolyn T. Dillon
      Recent studies showed that the metal-coordinated non-steroidal anti-inflammatory drug (NSAID), copper indomethacin, reduced aberrant crypt formation in the rodent colon cancer model, while also exhibiting gastrointestinal sparing properties. In the present study, the stability and biological activity of three BiNSAIDs of the general formula [Bi(L)3]n, where L=diflunisal (difl), mefenamate (mef) or tolfenamate (tolf) were examined. NMR spectroscopy of high concentrations of BiNSAIDs (24h in cell medium, 37°C) indicated that their structural stability and interactions with cell medium components were NSAID specific. Assessment of cell viability using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium]bromide (MTT) assay showed that the toxicity ranking of the BiNSAIDs paralleled those of the respective free NSAIDs: diflH<mefH<tolfH. While the IC50 values of the BiNSAIDs (ranging between 16 and 81μM) were lower than the free NSAIDs, it was apparent that the toxicity of the BiNSAIDs was due to the molar ratio of the three NSAID molecules contained in the BiNSAIDs, with the exception of [Bi(difl)3]. The highest cellular bismuth content was observed following treatment with [Bi(tolf)3]. Since NMR studies indicated that [Bi(tolf)3] was the most stable BiNSAID and that cellular uptake of bismuth correlated with structural stability it appears that bismuth uptake is assisted by the NSAID. Microprobe SR-XRF imaging showed that the intracellular fate of bismuth was independent of the specific BiNSAID treatment whereby all BiNSAID-treated cells showed bismuth accumulation in the cytoplasm within 24-h exposure. The size and location of the hot spots (0.3–5.8μm2), were consistent with cellular organelles such as lysosomes.
      Graphical abstract image

      PubDate: 2014-03-21T21:46:05Z
       
  • Disulfide bonds regulate binding of exogenous ligand to human cytoglobin
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135
      Author(s): Hirofumi Tsujino , Taku Yamashita , Azusa Nose , Kaori Kukino , Hitomi Sawai , Yoshitsugu Shiro , Tadayuki Uno
      Cytoglobin (Cgb) was discovered a decade ago and is a fourth member of the group of hexacoordinated globin-folded proteins. Although some crystal structures have been reported and several functions have been proposed for Cgb, its physiological role remains uncertain. In this study, we measured cyanide binding to the ferric state of the wild-type (WT) Cgb, and found that the binding consisted of multiple steps. These results indicated that Cgb may be comprised of several forms, and the presence of monomers, dimers, and tetramers was subsequently confirmed by SDS-PAGE. Remarkably, each species contained two distinguishable forms, and, in the monomer, analyses of alternative cysteine states suggested the presence of an intramolecular disulfide bond (monomer SS form) and a structure with unpaired thiol groups (monomer SH form). These confirmed that forms were separated by gel-exclusion chromatography, and that the cyanide binding of the separated fractions was again measured; they showed different affinities for cyanide, with the monomer fraction showing the highest affinity. In addition, the ferrous state in each fraction showed distinct carbon monoxide (CO)-binding properties, and the affinities for cyanide and CO suggested a linear correlation. Furthermore, we also prepared several variants involving the two cysteine residues. The C38S and C83S variants showed a binding affinity for cyanide similar to the value for the monomer SH form, and hence the fraction with the highest affinity for exogenous ligands was designated as a monomer SS form. We concluded that polymerization could be a mechanism that triggers the exertion of various physiological functions of this protein and that an appropriate disulfide bond between the two cysteine residues was critical for regulating the binding affinity of Cgb, which can act as a ROS scavenger, for exogenous ligands.
      Graphical abstract image

      PubDate: 2014-03-17T22:17:15Z
       
  • Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding,
           cytotoxicity, anti-inflammatory and anti-coagulant effects towards
           platelet activating factor
    • Abstract: Publication date: June 2014
      Source:Journal of Inorganic Biochemistry, Volume 135
      Author(s): Michael Kaplanis , George Stamatakis , Vasiliki D. Papakonstantinou , Maria Paravatou-Petsotas , Constantinos A. Demopoulos , Christiana A. Mitsopoulou
      The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione=1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV–visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1 promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20nM, respectively, whereas 1 affects PAF-catabolism.
      Graphical abstract image

      PubDate: 2014-03-17T22:17:15Z
       
  • Morphology-dependent bactericidal activities of Ag/CeO2 catalysts against
           Escherichia coli
    • Abstract: Publication date: Available online 11 March 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Lian Wang , Hong He , Yunbo Yu , Li Sun , Sijin Liu , Changbin Zhang , Lian He
      Silver-loaded CeO2 nanomaterials (Ag/CeO2) including Ag/CeO2 nanorods, nanocubes, nanoparticles were prepared with hydrothermal and impregnation methods. Catalytic inactivation of Escherichia coli with Ag/CeO2 catalysts through the formation of reactive oxygen species (ROS) was investigated. For comparison purposes, the bactericidal activities of CeO2 nanorods, nanocubes and nanoparticles were also studied. There was a 3-4 log order improvement in the inactivation of Escherichia coli with Ag/CeO2 catalysts compared with CeO2 catalysts. Temperature-programmed reduction of H2 showed that Ag/CeO2 catalysts had higher catalytic oxidation ability than CeO2 catalysts, which was the reason for that Ag/CeO2 catalysts exhibited stronger bactericidal activities than CeO2 catalysts. Further, the bactericidal activities of CeO2 and Ag/CeO2 depend on their shapes. Results of 5,5-dimethyl-1-pyrroline-N-oxide spin-trapping measurements by electron spin resonance and addition of catalase as a scavenger indicated the formation of •OH, •O2‾, and H2O2, which caused the obvious bactericidal activity of catalysts. The stronger chemical bond between Ag and CeO2 nanorods led to lower Ag+ elution concentrations. The toxicity of Ag+ eluted from the catalysts did not play an important role during the bactericidal process. Experimental results also indicated that Ag/CeO2 induced the production of intracellular ROS and disruption of the cell wall and cell membrane. A possible production mechanism of ROS and bactericidal mechanism of catalytic oxidation were proposed.
      Graphical abstract image

      PubDate: 2014-03-13T20:35:37Z
       
  • Antibacterial Properties of Water-Soluble Gold(I) N-heterocyclic Carbene
           Complexes
    • Abstract: Publication date: Available online 11 March 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Gabriela A. Fernández , María S. Vela Gurovic , Nelda L. Olivera , Alicia B. Chopa , Gustavo F. Silbestri
      The antibacterial properties of water-soluble gold(I) complexes [1-Methyl-3-(3-sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C1), [1-Mesityl-3-(3-sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C2), [1-(2,6-Diisopropylphenyl)-3-(3-sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C3) and [1,3-Bis(2,6-diisopropyl-4-sodiumsulfonatophenyl)imidazol-2-ylidene]gold(I) chloride (C4) and the respective ligands were assessed by agar diffusion and broth macrodilution methods against Gram-positives Staphylococcus aureus, Enterococcus faecalis and Micrococcus luteus; and the Gram-negative bacteria Yersinia ruckeri, Pseudomonas aeruginosa and Escherichia coli. Viability after treatments was determined by direct plate count. The bactericidal activity displayed by C1 and C3 was comparable to that of AgNO3.
      Graphical abstract image

      PubDate: 2014-03-13T20:35:37Z
       
  • Mechanism of reaction of chlorite with mammalian heme peroxidases
    • Abstract: Publication date: Available online 28 February 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Christa Jakopitsch , Katharina F. Pirker , Jörg Flemmig , Stefan Hofbauer , Denise Schlorke , Paul G. Furtmüller , Jürgen Arnhold , Christian Obinger
      This study demonstrates that heme peroxidases from different superfamilies react differently with chlorite. In contrast to plant peroxidases, like horseradish peroxidase (HRP), the mammalian counterparts myeloperoxidase (MPO) and lactoperoxidase (LPO) are rapidly and irreversibly inactivated by chlorite in the micromolar concentration range. Chlorite acts as efficient one-electron donor for Compound I and Compound II of MPO and LPO and reacts with the corresponding ferric resting states in a biphasic manner. The first (rapid) phase is shown to correspond to the formation of a MPO-chlorite high-spin complex, whereas during the second (slower) phase degradation of the prosthetic group was observed. Cyanide, chloride and hydrogen peroxide can block or delay heme bleaching. In contrast to HRP, the MPO/chlorite system does not mediate chlorination of target molecules. Irreversible inactivation is shown to include heme degradation, iron release and decrease in thermal stability. Differences between mammalian peroxidases and HRP are discussed with respect to differences in active site architecture and heme modification.
      Graphical abstract image

      PubDate: 2014-03-01T07:15:31Z
       
 
 
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