- Structural Differences and Redox Properties of Unsymmetric Diiron PDIxCy Complexes
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We present two bimetallic iron complexes, [Fe2(PDIeCy)(OTf)4] (1) and [Fe2(PDIpCy)(THF)(OTf)4] (2) coordinated by an unsymmetric ligand. The new ligand, PDIeCy (PDI = pyridyldiimine; e = ethyl; Cy = cyclam), is
- Hess, Corinna R.,Hofmann, Andreas J.,Jandl, Christian
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- Copper(ii) complexes ofN-propargyl cyclam ligands reveal a range of coordination modes and colours, and unexpected reactivity
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The coordination chemistry ofN-functionalised cyclam ligands has a rich history, yet cyclam derivatives with pendant alkynes are largely unexplored. This is despite the significant potential and burgeoning application ofN-propargyl cyclams and related com
- Counsell, Andrew J.,Yu, Mingfeng,Shi, Mengying,Jones, Angus T.,Batten, James M.,Turner, Peter,Todd, Matthew H.,Rutledge, Peter J.
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- Dual-Function Polymeric HPMA Prodrugs for the Delivery of miRNA
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An HPMA-based polymeric prodrug of a CXCR4 antagonist, AMD3465 (P-SS-AMD), was developed as a dual-function carrier of therapeutic miRNA. P-SS-AMD was synthesized by a copolymerization of HPMA with a methacrylamide monomer in which the AMD3465 was attached via a self-immolative disulfide linker. P-SS-AMD showed effective release of the parent AMD3465 drug following treatment with intracellular levels of glutathione (GSH). The AMD3465 was released in the cells and exhibited functional CXCR4 antagonism, demonstrated by inhibition of the CXCR4-mediated cancer cell invasion. Due to its cationic character, P-SS-AMD could form polyplexes with miRNA and mediate efficient transfection of miR-200c mimics to downregulate expression of a downstream target ZEB-1 in cancer cells. The combined P-SS-AMD/miR-200c polyplexes showed improved ability to inhibit cancer cell migration when compared with individual treatments. The reported findings validate P-SS-AMD as a dual-function delivery vector that can simultaneously deliver a therapeutic miRNA and function as a polymeric prodrug of CXCR4 antagonist.
- Peng, Zheng-Hong,Xie, Ying,Wang, Yan,Li, Jing,Oupicky, David
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- Biotin-tagged fluorescent sensor to visualize 'mobile' Zn2+ in cancer cells
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A cancer cell-targeting fluorescent sensor has been developed to image mobile Zn2+ by introducing a biotin group. It shows a highly selective response to Zn2+in vitro, no toxicity in cellulo and images 'mobile' Zn2+ specifically in cancer cells. We believe this probe has the potential to help improve our understanding of the role of Zn2+ in the processes of cancer initiation and development.
- Fang, Le,Trigiante, Giuseppe,Kousseff, Christina J.,Crespo-Otero, Rachel,Philpott, Michael P.,Watkinson, Michael
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- Tri-N-Boc-tetraazamacrocycle-nucleoside conjugates: Synthesis and anti- HIV activities
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As far as linear N-Boc-polyamines conjugates elicited remarkable anti- HIV activity, the synthesis and anti-HIV properties of cyclic N-Boc- polyamines conjugates such as tetraazamacro-cycle-nucleoside were studied. These new conjugates include an ester linkage between the two moieties. They were synthesized using Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate coupling reagent, in the case of N-alkyl polyazamacrocycle derivatives, or through direct condensation of the acyl chloride derivative with nucleoside in the case of Nacyl polyazamacrocycle compounds. None of the new conjugates presented anti-HIV activity greater than that of the corresponding parent nucleosides.
- Dessolin,Vlieghe,Bouygues,Medou,Quelever,Camplo,Chermann,Kraus
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- Covalent attachment of [Ni(alkynyl-cyclam)]2+ catalysts to glassy carbon electrodes
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Surface modification of glassy carbon electrodes (GCEs) with molecular electrocatalysts is an important step towards developing more efficient heterogeneous CO2 reduction materials. Here, we report direct anodic electrografting of [Ni(alkynyl-cyclam)]2+ catalysts to the surface of GCEs in one simple step using inexpensive earth-abundant chemicals. When modified, these electrodes show reversible electrochemistry in organic solvents with zero peak-to-peak separations (ΔE = 0) and non-diffusive I (V) profiles that are typical for heterogeneous redox materials. CPE of these electrodes showed enhanced formation of H2 gas relative to CO compared to homogeneous catalysts.
- Zhanaidarova, Almagul,Moore, Curtis E.,Gembicky, Milan,Kubiak, Clifford P.
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- Synthesis and evaluation of [99mTc]TcAMD3465 as a SPECT tracer for CXCR4 receptor imaging
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CXCR4 plays an important role in a number of immunological-based diseases and cancers. The development of radiotracers targeting CXCR4 can provide a valuable tool for the diagnosis and monitoring of conditions involving deregulation of the receptor. The i
- Wu, Yitian,Zhu, Hong,Zhang, Xiaojun,Yu, Peng,Gui, Yuan,Xu, Zhihong,Zhang, Jinming,Tian, Jiahe
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- A functional model for the cysteinate-ligated non-heme iron enzyme superoxide reductase (SOR)
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Superoxide reductases (SORs) are cysteine-ligated, non-heme iron enzymes that reduce toxic superoxide radicals (O2-). The functional role of the trans cysteinate, as well as the mechanism by which SOR reduces O2-, is unknown. Herein is described a rare example of a functional metalloenzyme analogue, which catalytically reduces superoxide in a proton-dependent mechanism, via a trans thiolate-ligated iron-peroxo intermediate, the first example of its type. Acetic-acid-promoted H2O2 release, followed by Cp2Co reduction, regenerates the active Fe(II) catalyst. The thiolate ligand and its trans positioning relative to the substrate are shown to contribute significantly to the catalyst's function, by lowering the redox potential, changing the spin state, and dramatically lowering the νFe-O stretching frequency well-below that of any other reported iron-peroxo, while leaving νO-O high, so as to favor superoxide reduction and Fe-O, as opposed to O-O, bond cleavage. Thus we provide critical insight into the relationship between the SOR structure and its function, as well as important benchmark parameters for characterizing highly unstable thiolate-ligated iron-peroxo intermediates. Copyright
- Kitagawa, Terutaka,Dey, Abhishek,Lugo-Mas, Priscilla,Benedict, Jason B.,Kaminsky, Werner,Solomon, Edward,Kovacs, Julie A.
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- Synthesis of cyclam-capped β-cyclodextrin-bonded silica particles for use as chiral stationary phases in capillary electrochromatography
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β-Cyclodextrin (β-CD) was anchored onto silica particles at its C(2) position, derivatized primarily at the C(6) position by treatment with bromoacetyl bromide, and finally reacted with two types of cyclams to form cyclam-capped β-CD-bonded silica particles. When used as chiral stationary phases in capillary electrochromatography, these novel bonded silica particles exhibited excellent enantioselectivities for chiral separations.
- Gong, Yinhan,Xue, Guoping,Xiang, Yanqiao,Bradshaw, Jerald S,Lee, Milton L,Lee, Hian Kee
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- Cyclam-Modified PEI for Combined VEGF siRNA Silencing and CXCR4 Inhibition to Treat Metastatic Breast Cancer
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Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the develop
- Zhou, Yiwen,Yu, Fei,Zhang, Feiran,Chen, Gang,Wang, Kaikai,Sun, Minjie,Li, Jing,Oupicky, David
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- POTENTIATION OF β-LACTAM ANTIBIOTICS AND β-LACTAM/β-LACTAMASE INHIBITOR COMBINATIONS AGAINST MULTIDRUG AND EXTENSIVELY DRUG-RESISTANT PSEUDOMONAS AERUGINOSA USING NON-RIBOSOMAL TOBRAMYCIN-CYCLAM CONJUGATES
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Herein, we describe the development of non-β-lactam-based potentiator molecules that synergize with β-lactam antibiotics and β-lactam-β-lactamase inhibitor combinations against MDR/XDR P. aeruginosa phenotypes. The compound comprises a chemical structure
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Page/Page column 6; 26
(2020/06/10)
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- Development of a nebramine-cyclam conjugate as an antibacterial adjuvant to potentiate β-lactam antibiotics against multidrug-resistant P. aeruginosa
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The β-lactams are the most widely used class of antibiotics due to their safety, effectiveness, and spectrum of activity. As a result of their ubiquitous usage, there has been a steady rise in β-lactam resistant Gram-negative bacteria, especially Pseudomo
- Ammeter, Derek,Idowu, Temilolu,Zhanel, George G.,Schweizer, Frank
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p. 816 - 826
(2019/08/27)
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- Small molecular PET photographic developer of target chemokine receptor CXCR4
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The invention relates to a small molecular PET photographic developer of a target chemokine receptor CXCR4 and a preparation method of the small molecular PET photographic developer. According to thesmall molecular PET photographic developer of the target
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Paragraph 0052; 0066-0068
(2020/01/08)
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- Ligustrazine derivative, and preparation method and applications thereof
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The invention provides a ligustrazine derivative, and a preparation method and applications thereof. The ligustrazine derivative is capable of treating IAA induced hypoxic injury, promoting neuron cell proliferation, promoting cell synapsis lengthening, and can be used for treating stroke and neurodegenerative diseases.
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Paragraph 0017; 0044; 0081; 0092; 0093; 0094
(2019/08/12)
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- Selective Displacement of a Scorpionand Triazole Ligand from Metallocyclam Complexes Visualised with NMR Spectroscopy
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Target-activated metal complexes (TAMCs) – complexes that remain benign until reaching a specific biomolecular target, binding to which then effects structural change that turns on cytotoxicity or other activity – hold considerable allure. The successful
- Wong, Joseph K.-H.,Proschogo, Nicholas,Todd, Matthew H.,Rutledge, Peter J.
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supporting information
p. 1075 - 1086
(2017/03/08)
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- Anti-HIV drug and preparation method therefor
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The invention discloses an anti-HIV drug and a preparation method therefor. According to the anti-HIV drug and the preparation method therefor disclosed by the invention, the anti-HIV drug is a Raltegravir derivative ester, the chemical name of which is as follows: N-(2'-(4'-(4'-fluorobenzyl carbamoyl)-1'-methyl-6'-oxo-1',6'-dihydropyrimidine-2'-yl)-5'-methyl-1',3',4'-oxadiazole-2'-formamide-5'-oxy-{5-[1,4,8,11-teraazamacrocycle myristyl]methyl}phenyl)-1,4,8,11-teraazamacrocycle myristyl}-R-carboxylic ester. Compared to Raltegravir, the anti-HIV drug shows obvious and relatively higher activity (EC50) and selectivity index (SI=EC50/CC50), and solubility of the anti-HIV drug is remarkably improved.
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Paragraph 0021
(2016/10/08)
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- ANTIBACTERIAL COMPOUNDS
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The invention relates to antibacterial compounds, methods for synthesis and use thereof in antibacterial applications.
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Page/Page column 42; 43; 44
(2014/10/15)
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- CXCR4 INHIBITING CARRIERS FOR NUCLEIC ACID DELIVERY
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The present invention generally relates to carriers including polymers and lipids that comprise a CXCR4 inhibiting moiety. More specifically, these carriers are biodegradable and can be bioreducible polymers that comprise a CXCR4 inhibiting moiety. These carriers can be suitable for delivery of nucleic acids to cells. These carriers and pharmaceutical compositions can be used to treat various conditions including cancers and inflammation conditions.
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Paragraph 0178-0180
(2014/09/03)
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- Novel monocyclam derivatives as HIV entry inhibitors: Design, synthesis, anti-HIV evaluation, and their interaction with the CXCR4 co-receptor
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The CXCR4 receptor has been shown to interact with the human immunodeficiency virus (HIV) envelope glycoprotein gp120, leading to fusion of viral and cell membranes. Therefore, ligands that can attach to this receptor represent an important class of therapeutic agents against HIV, thus inhibiting the first step in the cycle of viral infection: the virus-cell entry/ fusion. Herein we describe the in silico design, synthesis, and biological evaluation of novel monocyclam derivatives as HIV entry inhibitors. In vitro activity testing of these compounds in cell cultures against HIV strains revealed EC50 values in the low micromolar range without cytotoxicity at the concentrations tested. Docking and molecular dynamics simulations were performed to predict the binding interactions between CXCR4 and the novel monocyclam derivatives. A binding mode of these compounds is proposed which is consistent with the main existing site-directed mutagenesis data on the CXCR4 coreceptor. Moreover, molecular modeling comparisons were performed between these novel monocyclams, previously reported non-cyclam compounds from which the monocyclams are derived, and the well-known AMD3100 bicyclam CXCR4 inhibitors. Our results suggest that these three structurally diverse CXCR4 inhibitors bind to overlapping but not identical amino acid residues in the transmembrane regions of the receptor.
- Pettersson, Sofia,Perez-Nueno, Violeta I.,Mena, Maria Pau,Clotet, Bonaventura,Este, Jose A.,Borrell, Jose I.,Teixido, Jordi
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scheme or table
p. 1272 - 1281
(2011/02/21)
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- HETEROBIFUNCTIONAL INHIBITORS OF E-SELECTINS AND CXCR4 CHEMOKINE RECEPTORS
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Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.
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Page/Page column 12; 33
(2010/11/17)
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- Synthesis and DNA binding ability of cyclam-amino acid conjugates
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N-Substituted cyclam-amino acid conjugates have been synthesised both in solution and on the solid phase. The DNA binding affinity of these species has been studied: the nature of the amino acid strongly influences the change in melting temperature sugges
- Venkata Ramana,Watkinson, Michael,Todd, Matthew H.
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p. 3007 - 3010
(2008/12/23)
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- Copper(II) complexes of the tetraazamacrocyclic tertiary amide ligand alanyl-cyclam
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Hydrogen bonding to the electrically neutral tertiary carboxamide nitrogen atom of peptidyl-prolyl groups is known to facilitate the C-N bond rotation during peptide and protein folding. Since metal complexes with nitrogen-coordinated tertiary amide ligan
- Schickaneder, Christian,Heinemann, Frank W.,Alsfasser, Ralf
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p. 2357 - 2363
(2007/10/03)
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- Synthesis and anti-HIV properties of new hydroxyquinoline-polyamine conjugates on cells infected by HIV-1 LAV and HIV-1 BaL viral strains
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To find new derivatives that block different virus strains entry in cells bearing specific surface receptors represent an interesting challenge for medicinal chemists. Here, we report the synthesis and the anti-HIV properties of a new series of analogues based on the introduction of quinoline moiety on various polyamine backbones, including polyazamacrocycles. Three compounds 7, 8, and 10 of this series were found active on PBMCs cells infected by HIV-1 LAV or by HIV-1 BaL, in contrast the well-known reference compound 1a (AMD 3100) was found only active on HIV-1 LAV strain.
- Moret, Vincent,Dereudre-Bosquet, Nathalie,Clayette, Pascal,Laras, Younes,Pietrancosta, Nicolas,Rolland, Amandine,Weck, Clement,Marc, Sylvain,Kraus, Jean-Louis
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p. 5988 - 5992
(2007/10/03)
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- LIGANDS HAVING METAL BINDING ABILITY AND TARGETING PROPERTIES
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Ligands having a metal binding domain and a targeting domain are provided. The ligands can be used to target, inhibit, and catalytically degrade or inactivate a desired target. Methods of treating a disease or condition using the ligands are also provided.
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(2008/06/13)
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- Solid-Phase Assisted N-1 Functionalization of Azamacrocycles
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A simple solid-phase assisted strategy for the N-1 functionalization of azamacrocycles is described. Compounds such as cyclen, cyclam and piperazine can be selectively modified by temporary attachment to solid-phase resins providing an efficient and clean method to prepare biomedically interesting moieteies.
- Oliver, Morag,Jorgensen, Michael R.,Miller, Andrew D.
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p. 453 - 456
(2007/10/03)
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- A two-channel molecular dosimeter for the optical detection of copper(II)
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A cyclam-like macrocycle with an integrated push-pull chromophore selectively detects Cu2+ inclusion through both orange-to-yellow colour change and quenching of the green fluorescence.
- Boiocchi, Massimo,Fabbrizzi, Luigi,Licchelli, Maurizio,Sacchi, Donatella,Vazquez, Miguel,Zampa, Cristina
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p. 1812 - 1813
(2007/10/03)
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- Light-emitting molecular machines: pH-induced intramolecular motions in a fluorescent nickel(II) scorpionate complex.
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A cyclam-like macrocycle has been synthesized with a pendant arm containing a dansylamide group. In the corresponding nickel(II) complex, binding of the pendant arm to the metal is pH controlled. In particular, at pH 4.3, the sulfonamide group deprotonates and coordinates the NiII center, giving rise to a complex of trigonal bipyramidal stereochemistry, as shown by X-ray diffraction studies performed on the crystalline complex salt. At pH 7.5, an OH- ion binds the metal and a six-coordinate species forms. The binding-detachment of the pendant arm to/from the NiII center is signaled by changes in the emission properties of the dansyl subunit in the side chain; the fluorescence of this side chain is high when the pendant arm is not coordinated and low when the sulfonamide group is bound to the metal. The system investigated represents the prototype of a light-emitting molecular machine, driven by a pH change.
- Fabbrizzi, Luigi,Foti, Francesco,Licchelli, Maurizio,Maccarini, Paola M,Sacchi, Donatella,Zema, Michele
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p. 4965 - 4972
(2007/10/03)
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- Nitroimidazoles and hypoxia imaging: Synthesis of three Technetium-99m complexes bearing a nitroimidazole group: Biological results
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Several Tc-99m complexes were synthesized, substituted with a nitroimidazole group, in order to visualize hypoxic tissues. The complexes were tested on rats (isolated hearts) and showed no significant uptake under hypoxic conditions. (C) 2000 Elsevier Science Ltd.
- Riche, Francoise,Du Moulinet d'Hardemare, Amaury,Sepe, Sandrine,Riou, Laurent,Fagret, Daniel,Vidal, Michel
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- New bicyclam-AZT conjugates: Design, synthesis, anti-HIV evaluation, and their interaction with CXCR-4 coreceptor
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We report the synthesis of mono- and bis-tetraazamacrocycle-AZT conjugates. All new compounds were screened for their ability to inhibit HIV- 1 replication in MT4 cell line and were compared to AZT alone. It appears that N-protected covalent prodrugs are
- Dessolin, Jean,Galea, Pascale,Vlieghe, Patrick,Chermann, Jean-Claude,Kraus, Jean-Louis
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p. 229 - 241
(2007/10/03)
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- Syntheses of new unsymmetrical bispolyazamacrocycles
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We report the synthesis of an original unsymmetrical bismacrocycle bearing a carboxylic side-arm. Two different synthetic pathways were investigated, both involving a Schotten-Baumann like reaction. The first route allowed us to obtain a mixture of compounds whilst the second one was direct and non-ambiguous.
- Dessolin,Quelever,Camplo,Kraus
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p. 853 - 856
(2007/10/03)
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- New facile and convenient synthesis of bispolyazamacrocycles using Boc protection. Determination of geometric parameters of dinuclear copper(II) complexes using ESR spectroscopy and molecular mechanics calculations
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A new facile and convenient synthetic route has been designed for the preparation of bispolyazamacrocycles in high yields by direct condensation of the readily available intermediate //,W-diboctriazamacrocycle or N,N',N"triboctetraazamacrocycles with aromatic biselectrophiles, ie, o-, m-, p-xylyl and anthracenyl derivatives. The use of a versatile group, such as ferf-butyloxycarbonyl (Boc), which is easily removed within l h by treatment with 6 M HC1 or TFA, leads to polyazamacrocycles in which one nitrogen is discriminated from the others. The anthracenyl and o-xylyl dimers were synthesized by reacting diacyl chloride to give the corresponding diamides. Further reduction of the amide groups and elimination of the protecting Boc moieties were carried in a one-pot reaction with BHa-THF followed by acid treatment. In parallel, exclusive mono-JV-alkylation of the available secondary amine of the same protected macrocycle with the corresponding dibromoxylene gave the meta and para dimers; the protecting moieties were eliminated in a similar way. ESR measurements of spin-spin distances of the dicopper complexes were determined from the ratio of the intensity of the forbidden transition to the intensity of the allowed transitions. Molecular mechanics calculations were also undertaken in order to evaluate the Cu-Cu distance by using a new rule-based force field. Eisevier,.
- Brandes, Stephane
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- Characterization and application of a new diprotected cyclam: A novel two-step synthesis of linked tetraazamacrocycles
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The synthesis and separation of the 1,8-di-(tertbutyloxycarbonyl) cyclam (1,8-diboc cyclam) among other isomers allow the facile obtention of singly or doubly linked, and bridged tetraazamacrocycles within a two-step synthesis in a very convenient way. This strategy can be applied to a large scale preparation of several types of dioxygen carriers or activators.
- Boitrel, Bernard,Andrioletti, Bruno,Lachkar, Mohammed,Guilard, Roger
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p. 4995 - 4998
(2007/10/02)
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