Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand.
Abstract Ruthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(η(6)-p-cymene)(L(1-7))Cl] were synthesized and characterized, of which the complex with L=isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by IC50 values determined after 48h of incubation (45.4±3.0 vs. 84.2±5.7μM, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 popul...
Source: Journal of Inorganic Biochemistry - April 13, 2016 Category: Biochemistry Authors: Jovanović KK, Tanić M, Ivanović I, Gligorijević N, Dojčinović BP, Radulović S Tags: J Inorg Biochem Source Type: research

Influence of chelation strength and bacterial uptake of gallium salicylidene acylhydrazide on biofilm formation and virulence of Pseudomonas aeruginosa.
t M Abstract Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on...
Source: Journal of Inorganic Biochemistry - April 13, 2016 Category: Biochemistry Authors: Hakobyan S, Rzhepishevska O, Björn E, Boily JF, Ramstedt M Tags: J Inorg Biochem Source Type: research

Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells.
ambert IH Abstract Acquired resistance to chemotherapeutic drugs in cancer cells can reflect an ability to limit cellular drug availability, to repair drug induced DNA damage, and to limit initiation/progression of cell death (apoptosis). The leucine-rich-repeat-containing 8A (LRRC8A) protein is an essential component of volume sensitive channels for organic osmolytes (VSOAC) and volume regulated anion channels (VRAC), which are activated during the apoptotic process. Here we illustrate that cisplatin resistance in human ovarian cancer cells (A2780) correlates with a reduced expression of LRRC8A and copper transpo...
Source: Journal of Inorganic Biochemistry - April 12, 2016 Category: Biochemistry Authors: Sørensen BH, Dam CS, Stürup S, Lambert IH Tags: J Inorg Biochem Source Type: research

Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.
In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 an...
Source: Journal of Inorganic Biochemistry - April 12, 2016 Category: Biochemistry Authors: Kan WC, Lu TL, Ling P, Lee TH, Cho CY, Huang CF, Jeng WY, Weng YP, Chiang CY, Wu JB, Lu TJ Tags: J Inorg Biochem Source Type: research

Coordination and redox properties of copper interaction with α-synuclein.
Coordination and redox properties of copper interaction with α-synuclein. J Inorg Biochem. 2016 Apr 11; Authors: Valensin D, Dell'Acqua S, Kozlowski H, Casella L Abstract Parkinson's disease (PD) is a severe neurodegenerative disorder affecting movements. After Alzheimer's disease, it is the most common form of neurodegeneration. PD is characterized by the loss of neurons producing dopamine and by the presence of protein aggregates in the brain, known as Lewy bodies. The main constituent of Lewy bodies is the misfolded form of α-synuclein (αSyn), able to form oligomers and fibrils. I...
Source: Journal of Inorganic Biochemistry - April 10, 2016 Category: Biochemistry Authors: Valensin D, Dell'Acqua S, Kozlowski H, Casella L Tags: J Inorg Biochem Source Type: research

Insights into molecular mechanism of action of salan titanium(IV) complex with in vitro and in vivo anticancer activity.
Abstract Titanium compounds, in particular, Ti(IV) based diaminobis(phenolato) "salan" complexes demonstrate high cytotoxicity towards a wide range of cancer cell lines in vitro, and still, very little is known on their mode of action. A representative salan Ti(IV) complex was tested both in vitro and in vivo on human HT-29 colorectal adenocarcinoma and A2780 ovarian carcinoma cells. Both cell lines were sensitive in vitro with A2780 demonstrating an enhanced rate of uptake and intracellular accumulation and thus an earlier response to the drug. HT-29 cells responded in vivo by impaired tumor development...
Source: Journal of Inorganic Biochemistry - April 8, 2016 Category: Biochemistry Authors: Miller M, Braitbard O, Hochman J, Tshuva EY Tags: J Inorg Biochem Source Type: research

The role of the equatorial ligands for the redox behavior, mode of cellular accumulation and cytotoxicity of platinum(IV) prodrugs.
BK Abstract The current study aims to elucidate the possible reasons for the significantly different pharmacological behavior of platinum(IV) complexes with cisplatin-, carboplatin- or nedaplatin-like cores and how this difference can be related to their main physicochemical properties. Chlorido-containing complexes are reduced fast (within hours) by ascorbate and are able to unwind plasmid DNA in the presence of ascorbate, while their tri- and tetracarboxylato analogs are generally inert under the same conditions. Comparison of the lipophilicity, cellular accumulation and cytotoxicity of the investigated platinu...
Source: Journal of Inorganic Biochemistry - March 16, 2016 Category: Biochemistry Authors: Göschl S, Varbanov HP, Theiner S, Jakupec MA, Galanski M, Keppler BK Tags: J Inorg Biochem Source Type: research

Thermodynamics of the formation of Ag(I)-mediated azole base pairs in DNA duplexes.
ml;ller J Abstract Isothermal titration calorimetry was applied to determine the thermodynamic parameters for the specific binding of Ag(I) ions to a series of DNA duplexes comprising Im:Im or Tr:Tr mispairs to form metal-mediated Im-Ag(I)-Im or Tr-Ag(I)-Tr base pairs (Im=imidazole nucleoside; Tr=1.2,4-triazole nucleoside). A total of seven different duplexes are discussed, incorporating one to three artificial base pairs in neighboring or non-neighboring positions. The association constant related to the formation of Tr-Ag(I)-Tr base pairs is estimated to be
Source: Journal of Inorganic Biochemistry - March 15, 2016 Category: Biochemistry Authors: Schweizer K, Léon JC, Ravoo BJ, Müller J Tags: J Inorg Biochem Source Type: research

Engineering nitric oxide synthase chimeras to function as NO dioxygenases.
Abstract Nitric oxide synthases (NOSs) catalyze a two-step oxidation of l-arginine to form nitric oxide (NO) and l-citrulline. NOS contains a N-terminal oxygenase domain (NOSoxy) that is the site of NO synthesis, and a C-terminal reductase domain (NOSred) that binds nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN) and provides electrons to the NOSoxy heme during catalysis. The three NOS isoforms in mammals inducible NOS (iNOS), neuronal NOS (nNOS), and endothelial NOS (eNOS) share high structural similarity but differ in NO release rates and ca...
Source: Journal of Inorganic Biochemistry - March 14, 2016 Category: Biochemistry Authors: Wang ZQ, Haque MM, Binder K, Sharma M, Wei CC, Stuehr DJ Tags: J Inorg Biochem Source Type: research

The Inorganic Perspective of VEGF: Interactions of Cu(2+) with Peptides Encompassing a Recognition Domain of the VEGF Receptor.
lli E Abstract The vascular endothelial growth factor A (VEGF-A) is a potent angiogenic factor, its activity may be influenced by the presence of copper(II) ions. To mimic the interaction between copper(II) and VEGF (Vascular Endotelial Growth Factor), the N- and C-terminally blocked peptide fragments VEGF73-101 and VEGF84-101, owing to VEGF165 protein, have been synthesized. These protein domains represent a specific recognition site with the VEGF receptor (VEGFR). Copper(II) complexes with VEGF73-101 and VEGF84-101 were investigated by means of potentiometry and UV-Vis, ESI-MS, CD, EPR spectroscopic methods. Bot...
Source: Journal of Inorganic Biochemistry - March 14, 2016 Category: Biochemistry Authors: Grasso G, Santoro AM, Magrì A, La Mendola D, Tomasello MF, Zimbone S, Rizzarelli E Tags: J Inorg Biochem Source Type: research

Cadmium binding mechanisms of isolated domains of human MT isoform 1a: Non-cooperative terminal sites and cooperative cluster sites.
We report that the α-domain mechanism is driven by the cooperative formation of the Cd4MT cluster at slightly acidic pH (≤6.9) switching binding mechanisms over a physiologically relevant pH range, whereas the β-domain metalation mechanism is dominated by terminal coordination of cadmium in a non-cooperative manner above pH5.5. These results suggest that, in some acidic sub-cellular compartments, cadmium could be sequestered in the α-domain, leaving zinc or copper bound in the β-domain and available for donation to other metalloproteins. We propose that these results can be explained by the intrins...
Source: Journal of Inorganic Biochemistry - March 10, 2016 Category: Biochemistry Authors: Irvine GW, Stillman MJ Tags: J Inorg Biochem Source Type: research

Synthesis, characterization, and antitumor activity of three ternary dinuclear copper (II) complexes with a reduced Schiff base ligand and diimine coligands in vitro and in vivo.
In conclusion, these novel synthetic copper complexes have profound antitumor effects on human tumor cells and are promising therapeutic agents for human tumors. PMID: 26974885 [PubMed - as supplied by publisher] (Source: Journal of Inorganic Biochemistry)
Source: Journal of Inorganic Biochemistry - March 4, 2016 Category: Biochemistry Authors: Jia L, Xu J, Zhao X, Shen S, Zhou T, Xu Z, Zhu T, Chen R, Ma T, Xie J, Dong K, Huang J Tags: J Inorg Biochem Source Type: research

Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin.
ić M Abstract Hyphenated mass spectrometry (MS) techniques have attained an important position in analysis of covalent and non-covalent interactions of metal complexes with peptides and proteins. The aim of the present study was to qualitatively and quantitatively determine ruthenium binding sites on a protein using tandem mass spectrometry and allied techniques, i.e. liquid chromatography (LC) and inductively coupled plasma optical emission spectrometry (ICP-OES). For that purpose, two newly synthesized Ru(II) complexes of a meridional geometry, namely mer-[Ru(4' Cl-tpy)(en)Cl](+) (1) and mer-[Ru(4' Cl-tpy)(dach...
Source: Journal of Inorganic Biochemistry - March 2, 2016 Category: Biochemistry Authors: Nišavić M, Masnikosa R, Butorac A, Perica K, Rilak A, Korićanac L, Hozić A, Petković M, Cindrić M Tags: J Inorg Biochem Source Type: research

Tuning the geometry and biomimetic catalytic activity of manganese(III)-tetrabromocatecholate based robust platforms by introducing substitution at pyridine.
nja A Abstract The present report describes synthesis, characterization, crystal structures and catecholase activity of a series of five new manganese(III) complexes (1-5) derived from redox-noninnocent tetrabromocatecholate ligand in combination with different substituted pyridines. X-ray crystallography reveals that the geometry of manganese(III) centers in 1 and 2 is square pyramidal and they are pseudo-dimeric in the solid state resulting from the weak bonding of manganese(III) with a catecholate oxygen atom from the adjacent manganese(III) unit together with other weak interactions like hydrogen bonding and &...
Source: Journal of Inorganic Biochemistry - March 2, 2016 Category: Biochemistry Authors: Jana NC, Brandão P, Panja A Tags: J Inorg Biochem Source Type: research

On the ability of CuAβ1-x peptides to form ternary complexes: Neurotransmitter glutamate is a competitor while not a ternary partner.
On the ability of CuAβ1-x peptides to form ternary complexes: Neurotransmitter glutamate is a competitor while not a ternary partner. J Inorg Biochem. 2016 Mar 2; Authors: Frączyk T, Zawisza IA, Goch W, Stefaniak E, Drew SC, Bal W Abstract In the light of conflicting reports on the ability of copper(II) complexes of amyloid beta (Aβ) peptides to form ternary complexes with small molecules co-present in the biological milieu, we performed a study of coordination equilibria in the system containing Cu(II) ions, the Aβ1-16 peptide, glutamic acid and 4-(2-hydroxyethyl)-1-piperazineethanesu...
Source: Journal of Inorganic Biochemistry - March 2, 2016 Category: Biochemistry Authors: Frączyk T, Zawisza IA, Goch W, Stefaniak E, Drew SC, Bal W Tags: J Inorg Biochem Source Type: research

4-Azidobenzyl ferrocenylcarbamate as an anticancer prodrug activated under reductive conditions.
Abstract Aminoferrocene-based prodrugs are activated in the presence of cancer-specific amounts of reactive oxygen species, e.g. H2O2, with the formation of products of two types: Fe-containing complexes, which catalyze generation of HO and O2(-), and quinone methides, which alkylate glutathione and inhibit the antioxidative system of the cell. Both processes act synergistically by increasing the oxidative stress in cancer cells thereby leading to their death. However, in the activation step including the cleavage of a B-C bond one molecule of H2O2 is consumed that counteracts the desired effect of the products re...
Source: Journal of Inorganic Biochemistry - March 2, 2016 Category: Biochemistry Authors: Kinski E, Marzenell P, Hofer W, Hagen H, Raskatov JA, Knaup KX, Zolnhofer EM, Meyer K, Mokhir A Tags: J Inorg Biochem Source Type: research

Mitochondria-targeted ruthenium (II) polypyridyl complexes with benzofuran group for live cell imaging.
Abstract Labeling and imaging mitochondria have attracted considerable interest because of its involvement in early stage apoptosis and necrotic cell death. Various highly specific and photostable fluorescent probes for mitochondria are in demand. In the present study, two novel Ru(II) polypyridine complexes Ru1 and Ru2 were developed to act as mitochondrial fluorescence probes. In comparison with the commercially available mitochondrial trackers, Ru1 possesses high mitochondria-specificity, superior photostability, high resistance to the loss of mitochondrial membrane potential and appreciable tolerance to enviro...
Source: Journal of Inorganic Biochemistry - March 2, 2016 Category: Biochemistry Authors: Xu L, Liu YY, Chen LM, Xie YY, Liang JX, Chao H Tags: J Inorg Biochem Source Type: research

HENRYK - An endless source of metal coordination surprises.
Abstract The basic knowledge about biological inorganic chemistry, thermodynamics and metal binding sites of metalloproteins is crucial for the understanding of their metal binding-structure-function relationship. Metal-peptide complexes are useful and commonly used models of metal-enzyme active sites, among which copper and zinc models are one of the most extensively studied. HENRYK is a peptide sequence present in numerous proteins, and serves as a potentially tempting binding site for Cu(2+) and Zn(2+). Maybe more importantly, HENRYK also happens to be the first name of our group leader. The results of this wor...
Source: Journal of Inorganic Biochemistry - February 28, 2016 Category: Biochemistry Authors: Kołkowska P, Hecel A, Kędzierska D, Ostrowska M, Walencik PK, Wątły J, Zdyb K, Spodzieja M, Rodziewicz-Motowidło S, Potocki S, Łuczkowski M, Gumienna-Kontecka E, Rowińska-Żyrek M Tags: J Inorg Biochem Source Type: research

Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A.
Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A. J Inorg Biochem. 2016 Feb 27; Authors: Pelillo C, Mollica H, Eble JA, Grosche J, Herzog L, Codan B, Sava G, Bergamo A Abstract NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium-based drug characterised by the selective activity against tumour metastases. Previously we have shown the influence of the hepatic microenvironment to direct the arrest of the metastatic cells of colorectal cancer. Here we used the experimental m...
Source: Journal of Inorganic Biochemistry - February 27, 2016 Category: Biochemistry Authors: Pelillo C, Mollica H, Eble JA, Grosche J, Herzog L, Codan B, Sava G, Bergamo A Tags: J Inorg Biochem Source Type: research

Endocytosis of the tachykinin neuropeptide, neurokinin B, in astrocytes and its role in cellular copper uptake.
Abstract The tachykinin neuropeptide, neurokinin B (NKB), belongs to a family of peptides having diverse roles in the brain. NKB, along with several other tachykinins, has been identified as a copper-binding peptide, however the physiological relevance of the binding is unclear. Previously, NKB was shown to limit the ability of copper to enter astrocytes and disrupt calcium homeostasis and it was thought that the peptide was sequestering the metal extracellularly. Here we use a fluorescein-labelled NKB peptide (F-NKB) to show that NKB is not retained extracellularly, but is endocytosed within 10-20min after additi...
Source: Journal of Inorganic Biochemistry - February 27, 2016 Category: Biochemistry Authors: Shahzad R, Jones MR, Viles JH, Jones CE Tags: J Inorg Biochem Source Type: research

Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes (PTA=1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties.
Abstract Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA=1,3,5-triaza-7-phosphaadamantane, X=Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH=PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind=indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was also prepared and similarly investigated. Notably, ...
Source: Journal of Inorganic Biochemistry - February 16, 2016 Category: Biochemistry Authors: Battistin F, Scaletti F, Balducci G, Pillozzi S, Arcangeli A, Messori L, Alessio E Tags: J Inorg Biochem Source Type: research

Glycosidase- and β-lactamase-like activity of dinuclear copper(II) patellamide complexes.
This study reports their β-lactamase as well as α- and β-glycosidase activity with kcat=(11.34±0.91)ˑ10(-4)s(-1) for β-lactamase, kcat=(1.55±0.13)ˑ10(-4)s(-1) for α-glycosidase and kcat=(1.22±0.09)ˑ10(-4)s(-1) for β-glycosidase activity. PMID: 26921720 [PubMed - as supplied by publisher] (Source: Journal of Inorganic Biochemistry)
Source: Journal of Inorganic Biochemistry - February 13, 2016 Category: Biochemistry Authors: Comba P, Eisenschmidt A, Kipper N, Schießl J Tags: J Inorg Biochem Source Type: research

A Mn(II) complex of boradiazaindacene (BODIPY) loaded graphene oxide as both LED light and H2O2 enhanced anticancer agent.
In this report, a photo-active Mn(II) complex of boradiazaindacene derivatives (Mn1) was used as a dioxygen generator under irradiation with LED light in water. Moreover, the in vitro biological evaluation for Mn1 and its loaded graphene oxide (herein called Mn1@GO) on HepG-2 cells in normal and hypoxic conditions has been performed. In particular, Mn1@GO can react with H2O2 resulting active anticancer species, which show high inhibition on both HepG-2 cells and CoCl2-treated HepG-2 cells (hypoxic cancer cells). The mechanism of LED light enhanced anticancer activity for Mn1@GO on HepG-2 cells was discussed. Our results sh...
Source: Journal of Inorganic Biochemistry - February 13, 2016 Category: Biochemistry Authors: Xu XL, Shao J, Chen QY, Li CH, Kong MY, Fang F, Ji L, Boison D, Huang T, Gao J, Feng CJ Tags: J Inorg Biochem Source Type: research

Protein-based ferrogels.
We present a novel synthesis in which hemoglobin and Fe(2+) react, in the presence of KNO3 and KOH, to produce protein microgels that contain magnetic iron oxide nanoparticles. The synthesis results in microgels with polymer properties (denaturing and glass transition temperatures) that are consistent with the dried protein. The iron oxide nanoparticles that exhibit an average diameter of 22nm, are ferrimagnetic, and display properties consistent with Fe3O4. The multiple functional capabilities displayed by these materials: biocompatibility, magnetism, dye uptake and controlled release, and other properties archetypal of h...
Source: Journal of Inorganic Biochemistry - February 12, 2016 Category: Biochemistry Authors: Mody P, Hart C, Romano S, El-Magbri M, Esson MM, Ibeh T, Knowlton ED, Zhang M, Wagner MJ, Hartings MR Tags: J Inorg Biochem Source Type: research

Unbound position II in MXCXXC metallochaperone model peptides impacts metal binding mode and reactivity: Distinct similarities to whole proteins.
Abstract The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I)-Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid oxidation of its complex; in contrast, the Thr peptide with the Cys-Cu(I)-Met coordination under neutral conditions demonstrated weaker and pH dependent binding. Studies with human antioxidant protein 1 (Atox1) and three of its mutants where S residues were repl...
Source: Journal of Inorganic Biochemistry - February 12, 2016 Category: Biochemistry Authors: Shoshan MS, Dekel N, Goch W, Shalev DE, Danieli T, Lebendiker M, Bal W, Tshuva EY Tags: J Inorg Biochem Source Type: research

Topoisomerase I inhibition and DNA cleavage by zinc, copper, and nickel derivatives of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol complexes exhibiting anti-proliferation and anti-metastasis activity.
Abstract Three transition metal derivatives (Zn, Cu, and Ni) of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol (L) were synthesized by the reaction of the metal salts with the Schiff base ligand in one pot. In the crystal structure of [Zn(L)Br], the Schiff base ligand binds to the metal center through its phenolate oxygen and imine nitrogen, and adopts a distorted tetrahedral geometry. These compounds were found to inhibit topoisomerase I (topo I) activity, induce DNA cleavage and show DNA binding activity. Moreover, these compounds were found to be cytotoxic towards several cancer cell lines (A2780, MCF-7, HT...
Source: Journal of Inorganic Biochemistry - February 11, 2016 Category: Biochemistry Authors: Lee SK, Tan KW, Ng SW Tags: J Inorg Biochem Source Type: research

Preparation, optical and electrochemical properties, and molecular orbital calculations of tetraazaporphyrinato ruthenium (II) bis(4-methylpyridine) fused with one to four diphenylthiophene units.
Abstract 2,5-Diphenyl-3,4-dicyanothiophene (1) and phthalonitrile (2) were mixed and treated with ruthenium (III) trichloride, 4-methylpyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in 2-ethoxyethanol at 135°C, to produce low-symmetrical tetraazaporphyrins (TAPs) (3), (4), (5), and (6) with one to three thiophene rings. Two thiophene-annelated tetraazaporphyrins were isolated as opposite and adjacent isomers 4 and 5. The structure of 3 was determined by X-ray crystallography, showing that the thiophene ring linked at the 3,4-positions on the tetraazaporphyrin scaffold deviates from the mean plane of th...
Source: Journal of Inorganic Biochemistry - January 28, 2016 Category: Biochemistry Authors: Kimura T, Murakami N, Suzuki E, Furuyama T, Nakahodo T, Fujihara H, Kobayashi N Tags: J Inorg Biochem Source Type: research

Synthesis, characterization, in vitro cytotoxicity and anticancer effects of ruthenium(II) complexes on BEL-7402 cells.
Abstract Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DQTT)](ClO4)2 (1) (DQTT=12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb=4,4'-dimethyl-2,2'-bipyridine), [Ru(bpy)2(DQTT)](ClO4)2 (2) (bpy=2,2'-bipyridine), [Ru(phen)2(DQTT)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(DQTT)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, (1)H NMR and (13)C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylt...
Source: Journal of Inorganic Biochemistry - January 22, 2016 Category: Biochemistry Authors: Zhang C, Han BJ, Zeng CC, Lai SH, Li W, Tang B, Wan D, Jiang GB, Liu YJ Tags: J Inorg Biochem Source Type: research

Bovine serum albumin binding, antioxidant and anticancer properties of an oxidovanadium(IV) complex with luteolin.
ms PA Abstract Chemotherapy using metal coordination compounds for cancer treatment is the work of the ongoing research. Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation, a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cation has been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na·3H2O (VOlut) were determined. The metal coordinated to two cis-deprotonated oxygen atoms (ArO(-)) of the ligand and two H2O molecules. Magnet...
Source: Journal of Inorganic Biochemistry - January 22, 2016 Category: Biochemistry Authors: Naso LG, Lezama L, Valcarcel M, Salado C, Villacé P, Kortazar D, Ferrer EG, Williams PA Tags: J Inorg Biochem Source Type: research

Complexation and molecular modeling studies of europium(III)-gallic acid-amino acid complexes.
Abstract With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the forma...
Source: Journal of Inorganic Biochemistry - January 21, 2016 Category: Biochemistry Authors: Taha M, Khan I, Coutinho JA Tags: J Inorg Biochem Source Type: research

The structures, cytotoxicity, apoptosis and molecular docking controlled by the aliphatic chain of palladium(II) complexes.
Abstract A new series of Pd(II) complexes derived from benzenealkyl dicarboxylate ligands, [Pd(Ln)(phen)] (phen=2,9-dimethyl-1,10-phenanthroline, complex 1: L1=phenylmalonate; complex 2: L2=benzylmalonate; complex 3: L3=(2-phenylethyl)malonate; complex 4: L4=(3-phenylpropyl)malonate) have been synthesized under room temperature condition. These complexes contain a long dicarboxylate aliphatic chain. They were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction. The binding of complexes with fish sperm DNA (FS-DNA) was investigated by UV absorption and fluorescence spectra. ...
Source: Journal of Inorganic Biochemistry - January 21, 2016 Category: Biochemistry Authors: Zhu M, Cui X, Zhang S, Liu L, Han Z, Gao E Tags: J Inorg Biochem Source Type: research

Apomaghemite as a doxorubicin carrier for anticancer drug delivery.
, Gálvez N Abstract Protein cages have well-defined structures and can be chemically and biologically engineered in many ways, making them useful platforms for drug delivery applications. Taking advantage of the unique structure feature of apoferritin, a new theranostic nanocarrier is proposed herein. The apoferritin protein is effective for the encapsulation of maghemite nanoparticles and for loading a significant dose of doxorubicin (DOX) drug. This simultaneous loading of maghemite nanoparticles and DOX has been achieved using either co-encapsulation or surface-binding approaches. Maghemite nanoparticles...
Source: Journal of Inorganic Biochemistry - January 21, 2016 Category: Biochemistry Authors: Jurado R, Frączek P, Droetto M, Sánchez P, Valero E, Domínguez-Vera JM, Gálvez N Tags: J Inorg Biochem Source Type: research

Catalytic reduction of dioxygen with modified Thermus thermophilus cytochrome c552.
Abstract Efficient catalysis of the oxygen reduction reaction (ORR) is of central importance to function in fuel cells. Metalloproteins, such as laccase (Cu) or cytochrome c oxidase (Cu/Fe-heme) carry out the 4H(+)/4e(-) reduction quite efficiently, but using large, complex protein frameworks. Smaller heme proteins also can carry out ORR, but less efficiently. To gain greater insight into features that promote efficient ORR, we expressed, characterized, and investigated the electrochemical behavior of six new mutants of cytochrome c552 from Thermus thermophilus: V49S/M69A, V49T/M69A, L29D/V49S/M69A, P27A/P28A/L29D...
Source: Journal of Inorganic Biochemistry - January 20, 2016 Category: Biochemistry Authors: Husband J, Aaron MS, Bains RK, Lewis AR, Warren JJ Tags: J Inorg Biochem Source Type: research

Toward a better understanding of the oxaliplatin mode of action upon the steric hindrance of 1,2-diaminocyclohexane and its analogue.
Abstract The present research is concerned with the mechanism investigation on the interaction between oxaliplatin and guanosine 5'-monophosphate (GMP) in the presence of glutathione (GSH). The binding modes of oxaliplatin with GMP and GSH were explored by HPLC and LC-MS techniques, respectively, in which four key intermediates were found and five adducts were determined in the reaction. The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways. One is by competing with GMP to bind the active platinum unit, and the other is by substituting the guanine-N7 atom of DNA to ...
Source: Journal of Inorganic Biochemistry - January 15, 2016 Category: Biochemistry Authors: Wang Z, Wu M, Gou S Tags: J Inorg Biochem Source Type: research

Synthesis, characterization and biological evaluation of novel Ru(II)-arene complexes containing intercalating ligands.
pka S Abstract Three new ruthenium(II)-arene complexes, namely [(η(6)-p-cymene)Ru(Me2dppz)Cl]PF6 (1), [(η(6)-benzene)Ru(Me2dppz)Cl]PF6 (2) and [(η(6)-p-cymene)Ru(aip)Cl]PF6 (3) (Me2dppz=11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine; aip=2-(9-anthryl)-1H-imidazo[4,5-f] [1,10] phenanthroline) have been synthesized and characterized using different spectroscopic techniques including elemental analysis. The complexes were found to be well soluble and stable in DMSO. The biological activity of the three complexes was tested in three different human cancer cell lines (A549, MDA-MB-231 and HeLa) and in one h...
Source: Journal of Inorganic Biochemistry - January 11, 2016 Category: Biochemistry Authors: Nikolić S, Rangasamy L, Gligorijević N, Aranđelović S, Radulović S, Gasser G, Grgurić-Šipka S Tags: J Inorg Biochem Source Type: research

ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.
Abstract Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (antioxidant protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as an in vitro model to evaluate if ATOX1 deficiency could af...
Source: Journal of Inorganic Biochemistry - January 11, 2016 Category: Biochemistry Authors: Barresi V, Spampinato G, Musso N, Trovato Salinaro A, Rizzarelli E, Condorelli DF Tags: J Inorg Biochem Source Type: research

One-dimensional chiral copper (II) complexes with novel nano-structures and superior antitumor activity.
Abstract Three novel copper(II) compounds of formulas {[Cu(Phen)(Ala)]·NO3·H2O}n (1), {[Cu(Phen)(Ala)]·NO3}n (2) and [Cu(Ala)2]n (3) have been synthesized and determined by X-ray diffraction. 1 and 2 are shown in one dimensional long-chain chiral structures, and 3 is a two dimensional checkerboard-type structure. Both 1 and 2 displayed a higher anticancer activity than 3 against various cancer cells, even higher than the similar mononuclear complexes and clinical anticancer drug 5-fluorouracil. The noncancerous cell lines (CCC-HEL-1) have showed that complexes 1-3 have hardly any cytotoxicity....
Source: Journal of Inorganic Biochemistry - January 11, 2016 Category: Biochemistry Authors: Zhang WC, Tang X, Lu X Tags: J Inorg Biochem Source Type: research

Distinct mechanisms for DNA cleavage by myoglobin with a designed heme active center.
This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can be fine-tuned by rational design of the heme active center with a hydrogen-bonding network. PMID: 26775281 [PubMed - as supplied by publisher] (Source: Journal of Inorganic Biochemistry)
Source: Journal of Inorganic Biochemistry - January 11, 2016 Category: Biochemistry Authors: Zhao Y, Du KJ, Gao SQ, He B, Wen GB, Tan X, Lin YW Tags: J Inorg Biochem Source Type: research

Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA G-quadriplex and exhibit anti-tumour activity.
Abstract G-quadruplex DNA, especially the cellular-myelocytomatosis viral oncogene (c-MYC) is closely associated with cell-cycle regulation, proliferation of tumour cells. In this work, the interaction between the c-MYC and two dinuclear Ru(II) complexes [(bpy)2Ru(bpibp)Ru(bpy)2](ClO4)4 (compound 1) and [(phen)2Ru(bpibp)Ru(phen)2](ClO4)4 (compound 2) have been studied. The data from UV-Visible, PCR-stop and Fluorescence resonance energy transfer (FRET) showed that two complexes can stabilize the structure of G-quadruplex in the c-MYC promoter and targeting the G-quadruplex loop isomers. Interestingly, the complex ...
Source: Journal of Inorganic Biochemistry - January 11, 2016 Category: Biochemistry Authors: Zheng C, Liu Y, Liu Y, Qin X, Zhou Y, Liu J Tags: J Inorg Biochem Source Type: research

The use of isomeric testosterone dimers to explore allosteric effects in substrate binding to cytochrome P450 CYP3A4.
Kincaid JR Abstract Cytochrome P450 CYP3A4 is the main drug-metabolizing enzyme in the human liver, being responsible for oxidation of 50% of all pharmaceuticals metabolized by human P450 enzymes. Possessing a large substrate binding pocket, it can simultaneously bind several substrate molecules and often exhibits a complex pattern of drug-drug interactions. In order to better understand structural and functional aspects of binding of multiple substrate molecules to CYP3A4 we used resonance Raman and UV-VIS spectroscopy to document the effects of binding of synthetic testosterone dimers of different configuration...
Source: Journal of Inorganic Biochemistry - December 31, 2015 Category: Biochemistry Authors: Denisov IG, Mak PJ, Grinkova YV, Bastien D, Bérubé G, Sligar SG, Kincaid JR Tags: J Inorg Biochem Source Type: research

The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2.)
Abstract A new ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2+) (Ru1, p-cpip=2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, MeIm=1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, Comet assay, inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 di...
Source: Journal of Inorganic Biochemistry - December 31, 2015 Category: Biochemistry Authors: Chen LM, Peng F, Li GD, Jie XM, Cai KR, Cai C, Zhong Y, Zeng H, Li W, Zhang Z, Chen JC Tags: J Inorg Biochem Source Type: research

Selective binding and magnetic separation of histidine-tagged proteins using Fe3O4/Cu-apatite nanoparticles.
Abstract Hierarchical Fe3O4@Cu-apatite nanoparticles (NPs) were synthesized via a facile hydrothermal method. The Fe3O4 cores present spherical shape and have a mean diameter of 300nm, and the Cu-apatite shell with thickness of about 50nm is composed of a large number of sheets. Using the high affinity of Cu(2+) on the surface toward histidine tags, the Fe3O4@Cu-apatite NPs can be applied to enrich and magnetically separate histidine tagged (His-tagged) proteins directly from the mixture of lysed cells. Research results indicated that the Fe3O4@Cu-apatite NPs presented negligible nonspecific protein adsorption and...
Source: Journal of Inorganic Biochemistry - December 30, 2015 Category: Biochemistry Authors: Li P, Li L, Zhao Y, Sun L, Zhang Y Tags: J Inorg Biochem Source Type: research

Comparative Raman study of four plant metallothionein isoforms: Insights into their Zn(II) clusters and protein conformations.
In conclusion, this work illustrates the attractive potential of Raman spectroscopy, combined with other techniques, to be a very informative tool for evidencing structural differences among in vivo synthesized metal-MT complexes. PMID: 26775276 [PubMed - as supplied by publisher] (Source: Journal of Inorganic Biochemistry)
Source: Journal of Inorganic Biochemistry - December 30, 2015 Category: Biochemistry Authors: Tomas M, Tinti A, Bofill R, Capdevila M, Atrian S, Torreggiani A Tags: J Inorg Biochem Source Type: research

Synthesis and structure elucidation of new μ-oxamido-bridged dicopper(II) complexes showing in vitro anticancer activity: Evaluation of DNA/protein-binding properties by experiment and molecular docking.
Synthesis and structure elucidation of new μ-oxamido-bridged dicopper(II) complexes showing in vitro anticancer activity: Evaluation of DNA/protein-binding properties by experiment and molecular docking. J Inorg Biochem. 2015 Dec 30;156:75-88 Authors: Zheng K, Liu F, Li YT, Wu ZY, Yan CW Abstract Two new μ-oxamido-bridged dicopper(II) complexes formulated as [Cu2(hmdoxd)(H2O)(Me2bpy)]-(ClO4)·DMF (1) and [Cu2(hmdoxd)(bpy)](ClO4)·CH3OH (2), where H3hmdoxd is N-(2-hydroxy-5-methylphenyl)-N'-[2-(dimethylamino)ethyl]oxamide; Me2bpy and bpy stand for 4,4'-dimethyl-2,2'-bipyridine and 2,2...
Source: Journal of Inorganic Biochemistry - December 30, 2015 Category: Biochemistry Authors: Zheng K, Liu F, Li YT, Wu ZY, Yan CW Tags: J Inorg Biochem Source Type: research

Structural and functional effects of benzimidazole/thioether-copper complexes with antitumor activity on cell membranes and molecular models.
nzález-Ugarte AK Abstract Two cytotoxic copper(II) complexes with N-H and N-methylated benzimidazole-derived ligands (Cu-L(2) and Cu-L(2Me)) were synthesized and made to interact with human erythrocytes and molecular models of their plasmatic membranes. The latter consisted in lipid bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), lipids of the types present in the outer and inner monolayers of the human erythrocyte membrane, respectively. Initial assessment of the interaction of the complexes with DMPC and DMPE consisted of X-ray diffraction studies, which s...
Source: Journal of Inorganic Biochemistry - December 30, 2015 Category: Biochemistry Authors: Castillo I, Suwalsky M, Gallardo MJ, Troncoso V, Sánchez-Eguía BN, Santiago-Osorio E, Aguiñiga I, González-Ugarte AK Tags: J Inorg Biochem Source Type: research

Characterization of the full-length btuB riboswitch from Klebsiella pneumoniae.
ver M Abstract Riboswitches are cis-regulatory RNA elements on the mRNA level that control the expression of the downstream coding region. The interaction of the riboswitch with its specific metabolite, which is related to the function of the controlled gene, induces a structural change of the RNA architecture. Consequently, gene regulation is induced by un/masking of the ribosome binding site (RBS). In the genome of Klebsiella pneumoniae a sequence was identified by bioinformatics and proposed to be a B12 riboswitch regulated by coenzyme B12. Here we study this new coenzyme B12-dependent riboswitch system by in-l...
Source: Journal of Inorganic Biochemistry - December 21, 2015 Category: Biochemistry Authors: Palou-Mir J, Musiari A, Sigel RK, Barceló-Oliver M Tags: J Inorg Biochem Source Type: research

New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions.
In conclusion the silver complex 1 is an anti-bacterial and non-genotoxic material, which can be applied to antibacterial drug in the future. PMID: 26765999 [PubMed - as supplied by publisher] (Source: Journal of Inorganic Biochemistry)
Source: Journal of Inorganic Biochemistry - December 19, 2015 Category: Biochemistry Authors: Sainis I, Banti CN, Owczarzak AM, Kyros L, Kourkoumelis N, Kubicki M, Hadjikakou SK Tags: J Inorg Biochem Source Type: research

Dimerization and DNA recognition rules of mithramycin and its analogues.
Abstract The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incomplete...
Source: Journal of Inorganic Biochemistry - December 18, 2015 Category: Biochemistry Authors: Weidenbach S, Hou C, Chen JM, Tsodikov OV, Rohr J Tags: J Inorg Biochem Source Type: research

Evaluation of employing poly-lysine tags versus poly-histidine tags for purification and characterization of recombinant copper-binding proteins.
Abstract Quantitative characterization of metalloproteins at molecular and atomic levels generally requires tens of milligrams of highly purified samples, a situation frequently challenged by problems in generating unmodified native forms. A variety of affinity tags, such as the popular poly-histidine tag, have been developed to facilitate purification but they generally rely on expensive affinity resins and their presence may interfere with protein characterization. This paper documents that addition of a poly-lysine tag to the C-terminus enables, for the copper-binding proteins examined, ready purification in la...
Source: Journal of Inorganic Biochemistry - December 18, 2015 Category: Biochemistry Authors: Wijekoon CJ, Ukuwela AA, Wedd AG, Xiao Z Tags: J Inorg Biochem Source Type: research

The inhibition of glycerol permeation through aquaglyceroporin-3 induced by mercury(II): A molecular dynamics study.
Abstract Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200ns in the presence of Hg(2+) ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg(2+) ions covalently bound to Cy...
Source: Journal of Inorganic Biochemistry - December 18, 2015 Category: Biochemistry Authors: Spinello A, de Almeida A, Casini A, Barone G Tags: J Inorg Biochem Source Type: research