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Journal of Inorganic Biochemistry
Elsevier Science Publishing Co.
Journal of Inorganic Biochemistry

Elsevier Science Publishing Co.

0162-0134

Journal of Inorganic Biochemistry/Journal Journal of Inorganic BiochemistrySCIISTPAHCI
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    Bio-inspired nitrogen oxide (NOx) interconversion reactivities of synthetic heme Compound-I and Compound-II intermediates

    Mondal, PritamTolbert, Garrett B.Wijeratne, Gayan B.
    12页
    查看更多>>摘要：Dioxygen activating heme enzymes have long predicted to be powerhouses for nitrogen oxide interconversion, especially for nitric oxide (NO) oxidation which has far-reaching biological and/or environmental impacts. Lending credence, reactivity of NO with high-valent heme-oxygen intermediates of globin proteins has recently been implicated in the regulation of a variety of pivotal physiological events such as modulating catalytic ac-tivities of various heme enzymes, enhancing antioxidant activity to inhibit oxidative damage, controlling in-flammatory and infectious properties within the local heme environments, and NO scavenging. To reveal insights into such crucial biological processes, we have investigated low temperature NO reactivities of two classes of synthetic high-valent heme intermediates, Compound-II and Compound-I. In that, Compound-II rapidly reacts with NO yielding the six-coordinate (NO bound) heme ferric nitrite complex, which upon warming to room temperature converts into the five-coordinate heme ferric nitrite species. These ferric nitrite complexes mediate efficient substrate oxidation reactions liberating NO; i.e., shuttling NO2back to NO. In contrast, Compound-I and NO proceed through an oxygen-atom transfer process generating the strong nitrating agent NO2, along with the corresponding ferric nitrosyl species that converts to the naked heme ferric parent complex upon warmup. All reaction components have been fully characterized by UV-vis, 2H NMR and EPR spectroscopic methods, mass spectrometry, elemental analyses, and semi-quantitative determination of NO2anions. The clean, efficient, potentially catalytic NOx interconversions driven by high-valent heme species presented herein illustrate the strong prospects of a heme enzyme/O2/NOx dependent unexplored territory that is central to human physiology, pathology, and therapeutics
      原文链接:
    • NSTL
    • Elsevier

    Amelioration of enteric dysbiosis by polyoxotungstates in mice gut

    Chen, KunLiu, YuanLi, MuLiu, Lu...
    8页
    查看更多>>摘要：Here we show that Preyssler-type polyoxotungstates (Preyssler-type POTs, [NaP5W30O110](-14)) complexed with peptides can prevent the dysbiotic expansion of anaerobic bacteria of the Enterobacteriaceae family. In a dextran sulfate sodium (DSS)-induced colitis model, symptom remission of C57BL/6 J mice with colitis is achieved by orally treated with POT complexes. Ten days of daily administration of POT complexes reduces 5% body weight loss and the mRNA levels of proinflammatory markers (77% reduction for Il6, 73% reduction for Tnf, 91% reduction for Cxcl1) in the caecum and proximal colon. Bacterial population analysis reveals that these Enterobacteriaceae population in the caecal content decline by one order of magnitude after administration of POT complexes. POT complexes exert anti-inflammatory effects indirectly on the host immune system by inhi-bition of malignant expansion of anaerobic Enterobacteriaceae during gut inflammation. Furthermore, POTs show negligible effect on bacterial growth in vitro, healthy mice and their microbiota composition under ho-meostatic conditions. Rationally designed POT complexes will provide distinctive approach to improve enteric bacteria dysbiosis-associated gut inflammation by balancing bacterial communities.
      原文链接:
    • NSTL
    • Elsevier

    A functional model for quercetin 2,4-dioxygenase: Geometric and electronic structures and reactivity of a nickel(II) flavonolate complex

    Jeong, DonghyunSun, SeungwonMoon, DohyunCho, Jaeheung...
    8页
    查看更多>>摘要：Quercetin 2,4-dioyxgenase (QueD) has been known to catalyze the oxygenative degradation of flavonoids and quercetin. Recent crystallographic study revealed a nickel ion occupies the active site as a co-factor to support O2 activation and catalysis. Herein, we report a nickel(II) flavonolate complex bearing a tridentate macrocyclic ligand, [NiII(Me3-TACN)(Fl)(NO3)](H2O) (1, Me3-TACN = 1,4,7-trimethyl-1,4,7-triazacyclononane, Fl = 3hydroxyflavone) as a functional model for QueD. The flavonolatonickel(II) complex was characterized by using spectrometric analysis including UV-vis spectroscopy, electrospray ionization mass spectrometer (ESI-MS), infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance spectroscopy (NMR). The single crystal X-ray structure of 1 shows two isomers with respect to the direction of a flavonolate ligand. Two isomers commonly are in the octahedral geometry with a bidentate of flavonolate and a monodentate of nitrate as well as a tridentate binding of Me3-TACN ligand. The spin state of 1 is determined to be a triplet state based on the Evans' method. Interestingly, electronic configuration of 1 from density functional theory (DFT) calculations revealed that the two singly occupied molecular orbitals (SOMOs) lie energetically lower than the highest (doubly) occupied molecular orbital (HOMO), that is so-called the SOMO-HOMO level inversion (SHI). The HOMO shows an electron density localized in the flavonolate ligand, indicating that flavonolate ligand is oxidized first rather than the nickel center. Thermal degradation of 1 resulted in the formation of benzoic acid and salicylic acid, which is attributed to the oxygenation of flavonolate of 1.
      原文链接:
    • NSTL
    • Elsevier

    Copper in tumors and the use of copper-based compounds in cancer treatment

    da Silva, Daniela AlmeidaDe Luca, AnastasiaSquitti, RosannaRongioletti, Mauro...
    23页
    查看更多>>摘要：Copper homeostasis is strictly regulated by protein transporters and chaperones, to allow its correct distribution and avoid uncontrolled redox reactions. Several studies address copper as involved in cancer development and spreading (epithelial to mesenchymal transition, angiogenesis). However, being endogenous and displaying a tremendous potential to generate free radicals, copper is a perfect candidate, once opportunely complexed, to be used as a drug in cancer therapy with low adverse effects. Copper ions can be modulated by the organic counterpart, after complexed to their metalcore, either in redox potential or geometry and consequently reactivity. During the last four decades, many copper complexes were studied regarding their reactivity toward cancer cells, and many of them could be a drug choice for phase II and III in cancer therapy. Also, there is promising evidence of using 64Cu in nanoparticles as radiopharmaceuticals for both positron emission tomography (PET) imaging and treatment of hypoxic tumors. However, few compounds have gone beyond testing in animal models, and none of them got the status of a drug for cancer chemotherapy. The main challenge is their solubility in physiological buffers and their different and non-predictable mechanism of action. Moreover, it is difficult to rationalize a structure-based activity for drug design and delivery. In this review, we describe the role
      原文链接:
    • NSTL
    • Elsevier

    A [Pt(cis-1,3-diaminocycloalkane)Cl-2] analog exhibits hallmarks typical of immunogenic cell death inducers in model cancer cells

    Novohradsky, VojtechMarkova, LenkaKostrhunova, HanaKasparkova, Jana...
    8页
    查看更多>>摘要：The platinum drugs belong to prevailing chemotherapeutics used in the treatment of cancer. At present, however, the search for new anticancer metal-based drugs that operate by the mechanisms distinct from those of the conventional chemotherapeutics is very active. Furthermore, it has been demonstrated that cytotoxic chemotherapy and immunotherapy may exert a highly synergistic anticancer activity. Thus, the development of antitumor platinum and other metal-based drugs that exhibit cytostatic effects and concurrently elicit immunogenic cell death (ICD) has shown promise for cancer treatment. Notably, conventional platinum drug oxaliplatin ([Pt (1R,2R-DACH)(oxalate)], DACH = diaminocyclohexane) is a well-known agent that displays both cytostatic and immune responses. Moreover, it was also demonstrated that even minor derivatization of the unleaving cycloalkyl moiety in oxaliplatin might have a pronounced effect on its immunomodulatory activity. Here, we investigated how replacing the 1R,2R- diaminocyclohexane ring by 1,3-diaminocycloalkane (alkane = butane, pentane, or hexane) affects the ability to evoke secretion of damage-associated molecular patterns characteristic of ICD in model murine colorectal carcinoma cell line CT26. The results indicate that among the investigated [Pt (cis-1,3-diaminocycloalkane)Cl2] complexes, the complex containing the cyclobutyl moiety exhibits the hallmarks typical of ICD inducers. Thus, [Pt(cis-1,3-diaminocyclobutane)Cl2] may expand the spectrum of anticancer chemotherapeutics capable of inducing ICD in cancer cells and might be of interest for further (pre)clinical development.
      原文链接:
    • NSTL
    • Elsevier

    Mitochondria-targeted Pt(IV) prodrugs conjugated with an aggregation-induced emission luminogen against breast cancer cells by dual modulation of apoptosis and autophagy inhibition

    Su, YanTu, YingLin, HaiZhang, Guan-Dong...
    9页
    查看更多>>摘要：Theranostic anticancer agents with dual functions of diagnosis and therapy are in highly demand for breast cancer. Herein, a triphenylphosphonium (TPP)-decorated aggregation-induced emission (AIE)-based Pt(IV) prodrug ACPt was developed, which exhibited superior anticancer performance with novel anticancer mechanism of dual modulation of apoptosis and autophagy inhibition. The experimental data showed that ACPt induced increased reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP). The morphology and function of mitochondria were also severely damaged and ACPt showed strong inhibition to both mitochondrial and glycolytic bioenergetics. Moreover, DNA damage and cell cycle arrest in the S-phase were also observed after the ACPt treatment, eventually leading to the apoptosis and autophagy inhibition of cancer cells. Furthermore, ACPt also indicated excellent anti-proliferation activity in 3D multicellular tumor spheroids (MCTSs), suggesting the potential to inhibit solid tumors in vivo. Our observation demonstrated that ACPt could serve as a promising anticancer theranostic agent toward breast cancers for prodrug activation monitoring and image-guided chemotherapy.
      原文链接:
    • NSTL
    • Elsevier

    Synthesis, characterisation and biological activity of the ruthenium(II) complexes of the N-4-tetradentate (N-4-T-L), 1,6-di (2 '-pyridyl)-2,5-dibenzyl-2,5-diazahexane (picenBz(2))

    Bjelosevic, AleksandraSakoff, JennetteGilbert, JayneZhang, Yingjie...
    11页
    查看更多>>摘要：A series of complexes of the type rac-cis-beta-[Ru(N-4-TL)(N-2-bidentates)](2+) (where N-4-TL = 1,6-di(2'-pyridyl)-2,5-dibenzyl-2,5-diazahexane (picenBz(2), N-4-T-L-2) and N-2-bidentates = 1,10-phenanthroline (phen, Ru-2), dipyrido [3,2-d:2',3'[-f]quinoxaline (dpq, Ru-3), 7,8-dimethyl-dipyrido[3,2-a:2;,3'-c] phenazine (dppzMe2, Ru-4), 2phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBz, Ru-5), 2-(p-tolyl)-1H-imidazo[4,5-f][1,10]phenan-throline (phenpyrBzMe, Ru-6), 2-(4-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBzNO(2), Ru7), were synthesised and characterised and X-ray crystallography of Ru-5 obtained. The in vitro cytotoxicity assays revealed that Ru-6 was 5, 2 and 19-fold more potent than oxaliplatin, cisplatin, and carboplatin, respectively displaying an average GI(50) value of approximate to 0.76 mu M against a panel of 11 cancer cell lines.
      原文链接:
    • NSTL
    • Elsevier

    3,3 '-Diselenodipropionic acid (DSePA) forms 1:1 complex with Hg (II) and prevents oxidative stress in cultured cells and mice model

    Deshmukh, Y.Gandhi, V. V.Singh, B. G.Kumbhare, L. B....
    10页
    查看更多>>摘要：Mercury is one of the most toxic heavy metal for mammals particularly in inorganic form. In present study, 3,3'-diselenodipropionic acid (DSePA), a well-known pharmacological diselenide was evaluated for its interaction with HgCl2 and ability to prevent HgCl2-induced toxicity in experimental cellular and mice models. UV-visible, stopped flow, Fourier-transform infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy studies confirmed that DSePA sequestered Hg (II) ions with stoichiometry of 1:1 and binding constant of similar to 10(4) M-1. Xray photoelectron spectroscopy and X-ray powder diffraction analysis suggested that diselenide group of DSePA was involved in the complexation with Hg (II) ions. Further, Hg-DSePA complex degraded within 10 days to form excretable HgSe. The binding constant of DSePA and Hg (II) was comparable with that of dihydrolipoic acid, a standard disulfide compound used in heavy metal detoxification. Corroborating these observations, pretreatment of DSePA (10 mu M) significantly prevented the HgCl2 (50 mu M)-induced glutathione oxidation (GSH/ GSSG), decrease of thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities and cell death in Chinese Hamster Ovary (CHO) cells. Similarly, intraperitoneal administration of DSePA at a dosage of 2 mg/kg for 5 consecutive days prior to exposure of HgCl2 (1 mg/kg) significantly suppressed oxidative stress in renal and hepatic tissues of C57BL/6 mice. In conclusion, the protective effect of DSePA against Hg induced oxidative stress is attributed to its ability to rescue the activities of GPx, TrxR and GSH by sequestering Hg (II) ions. DSePA being a relatively safer selenium-compound for in vivo administration can be explored for mercury detoxification.
      原文链接:
    • NSTL
    • Elsevier

    LAM-1 from Lysobacter antibioticus: A potent zinc-dependent activity that inactivates beta-lactam antibiotics

    Stroek, RozanneWilson, LiamGoracke, WilliamKang, Taeuk...
    4页
    查看更多>>摘要：Resistance to beta-lactam antibiotics, including the "last-resort" carbapenems, has emerged as a major threat to global health. A major resistance mechanism employed by pathogens involves the use of metallo-beta-lactamases (MBLs), zinc-dependent enzymes that inactivate most of the beta-lactam antibiotics used to treat infections. Variants of MBLs are frequently discovered in clinical environments. However, an increasing number of such enzymes have been identified in microorganisms that are less impacted by human activities. Here, an MBL from Lysobacter antibioticus, isolated from the rhizosphere, has been shown to be highly active toward numerous beta-lactam antibiotics. Its activity is higher than that of some of the most effective MBLs linked to hospital-acquired antibiotic resistance and thus poses an interesting system to investigate evolutionary pressures that drive the emergence of such biocatalysts.
      原文链接:
    • NSTL
    • Elsevier

    Discovery and characterization of a novel Dyp-type peroxidase from a marine actinobacterium isolated from Trondheim fjord, Norway

    Cordas, Cristina M.Nguyen, Giang-SonValerio, Gabriel N.Jonsson, Malene...
    9页
    查看更多>>摘要：A new dye-decolorizing peroxidase (DyP) was discovered through a data mining workflow based on HMMER software and profile Hidden Markov Model (HMM) using a dataset of 1200 genomes originated from a Actinobacteria strain collection isolated from Trondheim fjord. Instead of the conserved GXXDG motif known for Dyp-type peroxidases, the enzyme contains a new conserved motif EXXDG which has been not reported before. The enzyme can oxidize an anthraquinone dye Remazol Brilliant Blue R (Reactive Blue 19) and other phenolic compounds such as ferulic acid, sinapic acid, caffeic acid, 3-methylcatechol, dopamine hydrochloride, and tannic acid. The acidic pH optimum (3 to 4) and the low temperature optimum (25 degrees C) were confirmed using both biochemical and electrochemical assays. Kinetic and thermodynamic parameters associated with the catalytic redox center were attained by electrochemistry.
      原文链接:
    • NSTL
    • Elsevier