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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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    NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy

    Tang, QiYu, Ya-TingZhang, Hai-LinWang, Yi...
    6页
    查看更多>>摘要：A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo [4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.
      原文链接:
    • NSTL
    • Elsevier

    MiR-144-3p targets STC1 to activate PI3K/AKT pathway to induce cell apoptosis and cell cycle arrest in selenium deficiency broilers

    Luo DongliuGu XuedieKhoso, Pervez AhmedHuang Xiaodan...
    8页
    查看更多>>摘要：Selenium (Se) is an indispensable trace element in vertebrate. Se deficiency can damage the immune system. Studies have shown that Se deficiency can cause immune organ damage by regulating the expression of microRNA. Bursa of Fabricius is a special immune organ in poultry. In order to explore the mechanism of bursa of Fabricius injury caused by Se deficiency and the role of miRNA in this process. Firstly, we established the Se deficient model of broilers in vivo and found that Se deficiency could induce apoptosis and cell cycle arrest of bursa of Fabricius cells through Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) pathway. Secondly, we inferred miRNA (miR-144-3p) and target gene Stanniocalcin 1 (STC1) that may regulate PI3K/AKT pathway through biological analysis system, and further predicted and determined the targeting relationship between them through dual luciferase, it was found that miR-144-3p was highly expressed in the process of cell apoptosis and cell cycle arrest induced by Se deficiency. Finally, in order to further understand whether miR-144-3p/STC1 axis is involved in the process, miR-144-3p knockdown and overexpression experiments were carried out, it was found that miR-144-3p inhibitor can reduce the occurrence of cell apoptosis and cell cycle arrest. In conclusion, Se deficiency can induce apoptosis and cell cycle arrest of bursa of Fabricius in Broilers by up regulating miR144-3p targeting STC1 and activating PI3K/AKT pathway, leading to injury of bursa of Fabricius in broilers.
      原文链接:
    • NSTL
    • Elsevier

    Ru(II)/amino acid complexes inhibit the progression of breast cancer cells through multiple mechanism-induced apoptosis

    Almeida, Marcio Aurelio P.Menck, Carlos F. M.Mello-Andrade, FrancyelliBatista, Alzir A....
    12页
    查看更多>>摘要：For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been developed to act in all steps of tumor growth and its progression. In this study, we investigated the effects of Ruthenium (II) complexes coupled to the amino acids methionine (RuMet) and tryptophan (RuTrp) on the induction of cell death, clonogenic survival ability, inhibition of angiogenesis, and migration of MDA-MB-231 cells (human triple-negative breast cancer). The study also demonstrated that the RuMet and RuTrp complexes induce cell cycle blockage and apoptosis of MDA-MB-231 cells, as evidenced by an increase in the number of Annexin V-positive cells, p53 phosphorylation, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Moreover, morphological changes and loss of mitochondrial membrane potential were detected. The RuMet and RuTrp complexes induced DNA damage probably due to reactive oxygen species production related to mitochondrial membrane depolarization. Therefore, the RuMet and RuTrp complexes acted directly on breast tumor cells, leading to cell death and inhibiting their metastatic potential; this reveals the potential therapeutic action of these drugs.
      原文链接:
    • NSTL
    • Elsevier

    Zinc(II) complexes of 3,5-dibromo-salicylaldehyde and a-diimines: Synthesis, characterization and in vitro and in silico biological profile

    Zianna, AriadniGeromichalou, ElenaGeromichalos, GeorgeFiotaki, Augusta-Maria...
    19页
    查看更多>>摘要：The synthesis of five neutral zinc(II) complexes of 3,5-dibromo-salicyladehyde (3,5-diBr-saloH) in the presence of nitrogen-donor co-ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) was undertaken and complexes [Zn(3,5-diBr-salo)(2)(H2O)(2)] (1), [Zn(3,5-diBr-salo)(2)(bipy)] (2), [Zn(3,5-diBr-salo)(2)(phen)].3,5-diBr-saloH (3), [Zn(3,5-diBr-salo)(2)(neoc)] (4) and [Zn(3,5-diBr-salo)(2)(bipyam)] (5) were characterized by various techniques. The crystal structures of complexes 3 and 5 were determined by X-ray crystallography, revealing the co-existence of two different coordination modes of 3,5-diBr-salo(-)& nbsp;ligands. The new complexes show selective in vitro antibacterial activity against two Gram-positive and two Gram-negative bacterial strains. The complexes may scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and reduce H2O2. The complexes may intercalate in-between the calf-thymus DNA-bases and have exhibited low-to-moderate ability to cleave supercoiled circular pBR322 plasmid DNA. The complexes may bind tightly and reversibly to bovine and human serum albumins. In order to explain the in vitro activity of the compounds, molecular docking studies were adopted on the crystal structure of calf-thymus DNA, human and bovine serum albumin, Escherichia coli and Staphylococcus aureus DNA-gyrase, 5-lipoxygenase, and 5-lipoxygenase activating protein. The employed in silico studies aimed to explore the ability of the compounds to bind to these target biomacromolecules, establishing a possible mechanism of action and were in accordance with the in vitro studies.
      原文链接:
    • NSTL
    • Elsevier

    Heteroleptic copper(II) complexes of prenylated flavonoid osajin behave as selective and effective antiproliferative and anti-inflammatory agents

    Vanco, JanTravnicek, ZdenekHosek, JanDvorak, Zdenek...
    12页
    查看更多>>摘要：Heteroleptic copper(II) complexes, containing prenylated flavonoid osajin isolated from the fruits of Maclura pomifera Schneid., were prepared and thoroughly characterized, including single crystal X-ray analysis. Some of the following complexes of the general composition [Cu(L)(bpy)]NO3 (1), [Cu(L)(dimebpy)]NO3.2MeOH (2) [Cu (L)(phen)]NO3.H2O (3), [Cu(L)(bphen)]NO3 (4) and [Cu(L)(dppz)]NO3 (5), where HL stands for 3-(4-hydrox-yphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one (osajin), bpy = 2,2 '-bipyridine, dimebpy = 4,4 '-dimethyl-2,2 '-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline and dppz = dipyrido[3,2-a:2',3'-c]phenazine, were also monitored for their so-lution stability and interactions with cysteine and glutathione by mass spectrometry. The in vitro cytotoxicity of the complexes was evaluated against a panel of eight human cancer cell lines: (MCF-7, HOS, A549, PC-3, A2780, A2780R, Caco-2, and THP-1). The results revealed high antiproliferative activity of the complexes with the best IC50 values of 0.5-3.4 mu M for complexes (4) and (5), containing the bulkier N,N'-donor ligands (bphen, and dppz, respectively). The complexes also revealed a relatively low toxicity towards human hepatocytes (IC50 values are higher than 100 mu M in some cases), and thus proved to be highly selective towards the cancer cells. On the other hand, the complexes showed a strong in vitro nuclease effect using the model pUC-19 plasmid. In the model of lipopolysaccharide-stimulated (LPS) THP-1 monocytes, the complexes revealed ability to lower the activity of nuclear factor kappa-B/activator protein 1 (NF-Kappa B /AP-1) system and decrease the secretion of tumor necrosis factor alpha (TNF-alpha). Thus, the complexes have been identified as strong antiproliferative and anti-inflammatory compounds.
      原文链接:
    • NSTL
    • Elsevier

    Screening of biological properties of MoV2O2S2- and MoV2O4-based coordination complexes: Investigation of antibacterial, antifungal, antioxidative and antitumoral activities versus growing of Spirulina platensis biomass

    Haouas, MohamedToderas, IonGulea, AurelianFloquet, Sebastien...
    10页
    查看更多>>摘要：This paper deals with the biological potential of coordination compounds based on binuclear core [MoV2O2E2]2+ (E = O or S) coordinated with commercially available ligands such as oxalates (Ox2- ), L-cysteine (L-cys2-), Lhistidine (L-his-), Iminodiacetate (IDA2-), Nitrilotriacetate (HNTA2- or NTA3-) or ethylenediamine tetraacetate (EDTA4-) by means of various in vitro assays in a screening approach. Results suggest that the obtained complexes show weak antibacterial and antifungal properties while not being cytotoxic on cancerous and mammalian cells. In contrast, [Mo2O2E2(L-cys)2]2- complexes stand out as powerful antioxidant, whereas [Mo2O2E2(EDTA)]2- associating tetraphenylphosphonium counter-cations display strong antibiotic activity. Finally, some complexes have evidenced a positive activity towards the growing of spirulina platensis together with a modification of the proportions of biological components inside the cells. These findings reveal promising bioactivity of the bridged binuclear Mo(+V) cores inside complexes and encourage further research for new highly active yet non-toxic molecules for biological and biomedical applications.
      原文链接:
    • NSTL
    • Elsevier

    Making and breaking carbon-carbon bonds in class C radical SAM methyltransferases

    Brimberry, Marley A.Mathew, LijuLanzilotta, William
    9页
    查看更多>>摘要：Radical S-adenosylmethionine (SAM) enzymes utilize a [4Fe-4S]1+ cluster and S-(5 '-adenosyl)-L-methionine, (SAM), to generate a highly reactive radical and catalyze what is arguably the most diverse set of chemical reactions for any known enzyme family. At the heart of radical SAM catalysis is a highly reactive 5 '-deoxyadenosyl radical intermediate (5 '-dAdo?) generated through reductive cleavage of SAM or nucleophilic attack of the unique iron of the [4Fe-4S]+ cluster on the 5 ' C atom of SAM. Spectroscopic studies reveal the 5 '-dAdo? is transiently captured in an Fe-C bond (0 species). In the presence of substrate, homolytic scission of this metal-carbon bond regenerates the 5 '-dAdo? for catalytic hydrogen atom abstraction. While reminiscent of the adenosylcobalamin mechanism, radical SAM enzymes appear to encompass greater catalytic diversity. In this review we discuss recent developments for radical SAM enzymes involved in unique chemical rearrangements, specifically regarding class C radical SAM methyltransferases. Illuminating this class of radical SAM enzymes is especially significant as many enzymes have been shown to play critical roles in pathogenesis and the synthesis of novel antimicrobial compounds.
      原文链接:
    • NSTL
    • Elsevier

    First evidence for N7-Platinated Guanosine derivatives cell uptake mediated by plasma membrane transport processes

    De Luca, ErikGirelli, Chiara RobertaBarca, AmilcareRomano, Alessandro...
    6页
    查看更多>>摘要：Nucleos(t)ide analogues (NA) belong to a family of compounds widely used in anticancer/antiviral treatments. They generally exhibit a cell toxicity limited by cellular uptake levels and the resulting nucleos(t)ides metabolism modifications, interfering with the cell machinery for nucleic acids synthesis. We previously synthesized purine nucleos(t)ide analogues N7-coordinated to a platinum centre with unaltered sugar moieties of the type: [Pt(dien) (N7-dGuo)](2+) (1; dien = diethylenetriamine; dGuo = 2'-deoxy-guanosine), [Pt(dien)(N7-dGMP)] (2; dGMP = 5'-(2'-deoxy)-guanosine monophosphate), and [Pt(dien)(N7-dGTP)]2-(3; dGTP = 5'-(2'-deoxy)-guanosine triphosphate), where the indicated electric charge is calculated at physiological pH (7.4). In this work, we specifically investigated the uptake of these complexes (1-3) at the plasma membrane level. Specific experiments on HeLa cervical cancer cells indicated a relevant cellular uptake of the model platinated deoxynucleos(t)ide 1 and 3 while complex 2 appeared unable to cross the cell plasma membrane. Obtained data buttress an uptake mechanism involving Na+-dependent concentrative transporters localized at the plasma membrane level. Consistently, 1 and 3 showed higher cytotoxicity with respect to complex 2 also suggesting selective possible applications as antiviral/antitumor drugs among the used model compounds.
      原文链接:
    • NSTL
    • Elsevier

    Moving Ru polypyridyl complexes beyond cytotoxic activity towards metastasis inhibition

    Brindell, MalgorzataGurgul, IlonaJanczy-Cempa, EwelinaGajda-Morszewski, Przemyslaw...
    10页
    查看更多>>摘要：In recent years, Ru polypyridyl complexes have been intensively studied for their anticancer activity. The vast majority of research focuses on assessing their cytotoxic activity, as well as targeting cancer cells with them. Since the formation of metastases poses a greater risk than primary tumors, scientists recently began evaluating these compounds as potential metastasis inhibitors. This review highlights the latest achievements in this field with particular attention to the identi-fication of the target proteins responsible for such activity. Cell migration, invasion, and adhesion are key components of metastasis, therefore understanding how they are affected by Ru polypyridyl complexes is of great importance.
      原文链接:
    • NSTL
    • Elsevier

    Distinct mechanism of action for antitumoral neutral cyclometalated Pt (II)-complexes bearing antifungal imidazolyl-based drugs

    Fernandez-Pampin, NataliaVaquero, MonicaGil, TaniaEspino, Gustavo...
    10页
    查看更多>>摘要：Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(kappa(2)-(C<^>N)Cl(L)], where C<^>N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one.
      原文链接:
    • NSTL
    • Elsevier