ChemMedChem

Cover image for Vol. 9 Issue 7

July 2014

Volume 9, Issue 7

Pages 1333–1615

  1. Cover Pictures

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
    1. You have free access to this content
      Cover Picture: Design, Synthesis and Bioevaluation of an EphA2 Receptor-Based Targeted Delivery System (ChemMedChem 7/2014) (page 1333)

      Dr. Elisa Barile, Dr. Si Wang, Dr. Swadesh K. Das, Dr. Roberta Noberini, Dr. Russell Dahl, Dr. John L. Stebbins, Prof. Elena B. Pasquale, Prof. Paul B. Fisher and Prof. Maurizio Pellecchia

      Version of Record online: 2 JUL 2014 | DOI: 10.1002/cmdc.201490024

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      The front cover picture shows that targeted delivery of Taxol (surface and stick representation) can be accomplished by conjugating the drug with a specific agent (green rod shape) targeting the membrane-anchored EphA2 receptor (orange). Binding of the drug conjugate causes receptor phosphorylation (indicated by a P) and internalization via endocytosis. The EphA2-bound drug conjugate is therefore actively internalized in the lysosomes where it gets cleaved delivering free Taxol. The EphA2 receptor is overexpressed in cancer cells and during angiogenesis. Therefore, drug conjugates targeting this receptor can selectively deliver chemotherapeutic agents to tumors and their vasculature. For more details, see the Full Paper by Maurizio Pellecchia et al. on p. 1403 ff.

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      Back Cover: The Integrin Ligand c(RGDf(NMe)Nal) Reduces Neointimal Hyperplasia in a Polymer-Free Drug-Eluting Stent System (ChemMedChem 7/2014) (page 1620)

      Dr. Florian Rechenmacher, Dr. Kristin Steigerwald, Dr. Burkhardt Laufer, Dr. Stefanie Neubauer, Tobias G. Kapp, Liang Li, Dr. Carlos Mas-Moruno, Dr. Michael Joner and Prof. Dr. Horst Kessler

      Version of Record online: 2 JUL 2014 | DOI: 10.1002/cmdc.201490027

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      The back cover picture shows the release of the peptidic integrin ligand c(RGDf(NMe)Nal) from a polymer-free drug-eluting stent to inhibit smooth muscle cell proliferation and as a consequence to reduce neointimal hyperplasia. For more details, see the Full Paper by Horst Kessler et al. on p. 1413 ff.

  2. Graphical Abstract

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
    1. You have free access to this content
  3. News

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
  4. Communications

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
    1. Efficiently Detecting Metallodrug–Protein Adducts: Ion Trap versus Time-of-Flight Mass Analyzers (pages 1351–1355)

      Dr. Samuel M. Meier, Maria V. Babak, Prof. Bernhard K. Keppler and Prof. Christian G. Hartinger

      Version of Record online: 18 MAR 2014 | DOI: 10.1002/cmdc.201400020

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      Weighing the alternatives: Mass spectrometry is increasingly employed for metallodrug–protein binding studies. However, a methodical investigation on mass analyzers and especially their influence on the efficiency of adduct detection has not been carried out so far. We show that mass analyzers can exhibit pronounced differences on adduct detection efficiencies, influencing investigations on potential cellular targets and for the screening of metallodrugs.

    2. Development and Screening of a Series of Antibody-Conjugated and Silica-Coated Iron Oxide Nanoparticles for Targeting the Prostate-Specific Membrane Antigen (pages 1356–1360)

      Dr. Amarnath Mukherjee, Dr. Thomas Darlington, Dr. Richard Baldwin, Charles Holz, Sage Olson, Dr. Prakash Kulkarni, Dr. Theodore L. DeWeese, Dr. Robert H. Getzenberg, Dr. Robert Ivkov and Dr. Shawn E. Lupold

      Version of Record online: 3 MAR 2014 | DOI: 10.1002/cmdc.201300549

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      Targeted MIONs: Silica-coated antibody-conjugated iron oxide nanoparticles were prepared, and their ability to specifically target prostate-specific membrane antigen (PSMA), a validated target in prostate cancer, was evaluated using iron spectral absorbance and enzyme-linked immunoassay (ELISA).

    3. Structural Optimization and Biological Screening of a Steroidal Scaffold Possessing Cucurbitacin-Like Functionalities as B-Raf Inhibitors (pages 1361–1367)

      Mahmoud S. Ahmed, Dr. Lucas C. Kopel and Prof. Dr. Fathi T. Halaweish

      Version of Record online: 28 MAR 2014 | DOI: 10.1002/cmdc.201300523

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      A hybrid scaffold: Molecular docking studies resulted in the design of hybrid compounds containing the α,β-unsaturated ketone of cucurbitacin D, a triterpene natural product, and an estrone core, along with a Δ9,11 olefin. When evaluated in A-375 mutant B-Raf cells, compounds with this combination of cucurbitacin-like and steroidal features exhibited potent inhibition of phosphorylated extracellular-signal-regulated kinase (ERK).

    4. Efficient Acid-Catalyzed 18F/19F Fluoride Exchange of BODIPY Dyes (pages 1368–1373)

      Dr. Edmund J. Keliher, Jenna A. Klubnick, Dr. Thomas Reiner, Dr. Ralph Mazitschek and Prof. Ralph Weissleder

      Version of Record online: 5 MAR 2014 | DOI: 10.1002/cmdc.201300506

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      A colorful exchange: In this study we explore acid-catalyzed 18F/19F exchange on a range of commercially available NHS ester and maleimide BODIPY fluorophores. We show this method to be a simple and efficient 18F-labeling strategy for a diverse range of fluorescent compounds, including a BODIPY-modified PARP-1 inhibitor, and amine- and thiol-reactive BODIPY fluorophores.

    5. Xanthones from Swertia mussotii as Multitarget-Directed Antidiabetic Agents (pages 1374–1377)

      Huan-Huan Zheng, Cui-Ting Luo, Prof. Heru Chen, Juan-Na Lin, Prof. Dr. Chun-Ling Ye, Shuang-Shuang Mao and Prof. Dr. Yu-Lin Li

      Version of Record online: 31 JAN 2014 | DOI: 10.1002/cmdc.201300507

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      Nature′s medicine cabinet: Xanthones isolated from Swertia mussotii were evaluated as multitarget antidiabetic agents. 1,3,5,8-Tetrahydroxylxanthone was identified as a good antioxidant, and also exhibited potent inhibition of α-glucosidase and aldose reductase, proven targets in the treatment of diabetes.

    6. The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile—Part 1 (pages 1378–1386)

      Thien Duc Tran, Florian Wakenhut, Dr. Chris Pickford, Stephen Shaw, Dr. Mike Westby, Caroline Smith-Burchnell, Lesa Watson, Michael Paradowski, Dr. Jared Milbank, Dr. Rebecca A. Brimage, Rebecca Halstead, Dr. Rebecca Glen, Dr. Craig P. Wilson, Fiona Adam, Duncan Hay, Jean-Yves Chiva, Carly Nichols, Dr. David C. Blakemore, Iain Gardner, Satish Dayal, Dr. Andrew Pike, Rob Webster and Dr. David C. Pryde

      Version of Record online: 11 APR 2014 | DOI: 10.1002/cmdc.201400045

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      Resisting resistance: An investigation into the anti-hepatitis C virus (HCV) replicon activity of a series of biaryl-linked pyrrolidine NS5A inhibitors explored a diverse range of core structure modifications as key determinants of antiviral activity and susceptibility to common resistance mutations. Further evaluation of several core structure designs identified a compound with excellent pharmacokinetics, suitable for once daily dosing.

    7. The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile—Part 2 (pages 1387–1396)

      Florian Wakenhut, Thien Duc Tran, Dr. Chris Pickford, Stephen Shaw, Dr. Mike Westby, Caroline Smith-Burchnell, Lesa Watson, Michael Paradowski, Dr. Jared Milbank, David Stonehouse, Dr. Kathy Cheung, Dr. Robert Wybrow, Dr. Felice Daverio, Dr. Samuel Crook, Keith Statham, Dr. David Leese, Dr. Darren Stead, Fiona Adam, Duncan Hay, Dr. Lee R. Roberts, Jean-Yves Chiva, Carly Nichols, Dr. David C. Blakemore, Gilles H. Goetz, Dr. Ye Che, Iain Gardner, Satish Dayal, Dr. Andrew Pike, Rob Webster and Dr. David C. Pryde

      Version of Record online: 11 APR 2014 | DOI: 10.1002/cmdc.201400046

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      Refining the resistance: An investigation into the anti-hepatitis C virus (HCV) replicon activity of a series of biaryl-linked prolinamide NS5A inhibitors explored intramolecular H-bonding and peripheral functional group topology as key determinants of activity and membrane permeability. Studies of several peripheral group molecular designs resulted in compounds with improved aqueous solubility and a unique resistance profile.

    8. Stereoselective Reduction of 1-O-Isopropyloxygenipin Enhances Its Neuroprotective Activity in Neuronal Cells from Apoptosis Induced by Sodium Nitroprusside (pages 1397–1401)

      Rikang Wang, Jian Yang, Sufen Liao, Gaokeng Xiao, Jun Luo, Lang Zhang, Peter J. Little, Prof. Heru Chen and Prof. Wenhua Zheng

      Version of Record online: 6 APR 2014 | DOI: 10.1002/cmdc.201400051

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      Remastering Chinese herbal medicine: Genipin is known to have neuroprotective activity but problematic stability under physiological conditions. Isomeric derivatives of isopropyloxygenipin, a synthetic genipin analogue, were synthesized by stereoselective reduction of the C6[DOUBLE BOND]C7 double bond and found to exhibit improved neuroprotective activity and stability over the parent compounds.

  5. Full Papers

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
    1. Design, Synthesis and Bioevaluation of an EphA2 Receptor-Based Targeted Delivery System (pages 1403–1412)

      Dr. Elisa Barile, Dr. Si Wang, Dr. Swadesh K. Das, Dr. Roberta Noberini, Dr. Russell Dahl, Dr. John L. Stebbins, Prof. Elena B. Pasquale, Prof. Paul B. Fisher and Prof. Maurizio Pellecchia

      Version of Record online: 26 MAR 2014 | DOI: 10.1002/cmdc.201400067

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      Ready, aim, fire! We investigated the chemical determinants responsible for the stability and degradation in plasma of an EphA2-based targeted delivery system that is constituted by receptor-targeting peptides conjugated with paclitaxel. We demonstrate that our agents are both long-lived in plasma and markedly decrease tumor size in a prostate cancer xenograft model.

    2. The Integrin Ligand c(RGDf(NMe)Nal) Reduces Neointimal Hyperplasia in a Polymer-Free Drug-Eluting Stent System (pages 1413–1418)

      Dr. Florian Rechenmacher, Dr. Kristin Steigerwald, Dr. Burkhardt Laufer, Dr. Stefanie Neubauer, Tobias G. Kapp, Liang Li, Dr. Carlos Mas-Moruno, Dr. Michael Joner and Prof. Dr. Horst Kessler

      Version of Record online: 6 APR 2014 | DOI: 10.1002/cmdc.201400078

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      A bold stent team: The integrin ligand c(RGDf(NMe)Nal) was developed for inhibition of smooth muscle cell proliferation after being released from a polymer-free drug-eluting stent system. The peptide successfully reduced in-stent restenosis in an in vivo rabbit iliac artery model in the absence of delayed vascular healing.

    3. Bis(dipyridophenazine)(2-(2′-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II) Hexafluorophosphate: A Lesson in Stubbornness (pages 1419–1427)

      Dr. Tanmaya Joshi, Vanessa Pierroz, Priv.-Doz. Dr. Stefano Ferrari and Prof. Dr. Gilles Gasser

      Version of Record online: 3 MAR 2014 | DOI: 10.1002/cmdc.201400029

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      The mitochondria count: Cytotoxicity and cellular localization studies reveal that structural modifications (lipophilicity, charge, and size-based) of a cytotoxic bis(dppz)-RuII complex [Ru(dppz)2(CppH)])PF6 (1) result in its cytotoxic potency being compromised. Overall, the results of this important structure–activity relationship strongly support our initial hypothesis that accumulation in mitochondria is crucial for 1 to exert its cytotoxic action.

    4. Synthetic and Biological Studies of Tubulin Targeting C2-Substituted 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins (pages 1428–1435)

      Robert Scott, Dr. Menuka Karki, Mary R. Reisenauer, Roberta Rodrigues, Dr. Ramesh Dasari, W. Ross Smith, Prof. Dr. Stephen C. Pelly, Prof. Dr. Willem A. L. van Otterlo, Prof. Dr. Charles B. Shuster, Prof. Dr. Snezna Rogelj, Prof. Dr. Igor V. Magedov, Prof. Dr. Liliya V. Frolova and Prof. Dr. Alexander Kornienko

      Version of Record online: 18 MAR 2014 | DOI: 10.1002/cmdc.201300532

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      Rigid(in) development! Novel analogues of marine alkaloid rigidins were prepared utilizing new synthetic methods developed for the construction of the pyrrolo[2,3-d]pyrimidine ring system. The compounds exhibited sub-micromolar to nanomolar antiproliferative potencies against drug-resistant cells, such as glioblastoma, melanoma and non-small-cell lung cancer.

    5. Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins (pages 1436–1452)

      Dr. Chengwen Yang, Sha Chen, Mi Zhou, Dr. Yan Li, Yangfeng Li, Zhengxi Zhang, Dr. Zhen Liu, Dr. Qian Ba, Dr. Jingquan Li, Prof. Hui Wang, Prof. Xiaomei Yan, Prof. Dawei Ma and Prof. Renxiao Wang

      Version of Record online: 29 APR 2014 | DOI: 10.1002/cmdc.201400058

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      Hopping to inhibition: Several sets of derivatives of a lead compound have been designed and synthesized by following the scaffold-hopping strategy, and active compounds containing a 3-phenylthiophene-2-sulfonamide core moiety have been obtained. The most potent compounds have sub-micromolar binding affinity to the antiapoptotic protein Mcl-1 and are effective apoptosis inducers in living cells.

    6. Cytotoxic Triosmium Carbonyl Clusters: A Structure–Activity Relationship Study (pages 1453–1457)

      Hui Zhi Shirley Lee, Prof. Weng Kee Leong, Dr. Siden Top and Dr. Anne Vessières

      Version of Record online: 20 JAN 2014 | DOI: 10.1002/cmdc.201300394

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      The land of Os(mium): A structure–activity relationship study of a series of triosmium carbonyl clusters revealed that good solubility and a vacant site are necessary for activity. The newly synthesized compounds were more selective toward estrogen receptor (ER)-negative breast cancer cells versus ER-positive cells, indicating a different biological target than for tamoxifen.

    7. Small-Molecule Inhibitors of AF6 PDZ-Mediated Protein–Protein Interactions (pages 1458–1462)

      Dr. Carolyn Vargas, Prof. Dr. Gerald Radziwill, Dr. Gerd Krause, Dr. Anne Diehl, Prof. Dr. Sandro Keller, Dr. Nestor Kamdem, Prof. Dr. Constantin Czekelius, Annika Kreuchwig, Dr. Peter Schmieder, Dr. Declan Doyle, Prof. Dr. Karin Moelling, Dr. Volker Hagen, Dr. Markus Schade and Prof. Dr. Hartmut Oschkinat

      Version of Record online: 25 MAR 2014 | DOI: 10.1002/cmdc.201300553

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      Magnum PPIs: Selective inhibition of PDZ-mediated protein–protein interactions has high therapeutic potential, but is a very challenging task. Herein we report the development of inhibitors that interfere with AF6 PDZ protein–ligand interactions as well as intracellular signaling and cell proliferation.

    8. Synthesis and Biological Evaluation of Imidazo[2,1-b][1,3,4]thiadiazole-Linked Oxindoles as Potent Tubulin Polymerization Inhibitors (pages 1463–1475)

      Dr. Ahmed Kamal, M. P. Narasimha Rao, Pompi Das, P. Swapna, Sowjanya Polepalli, Vijaykumar D. Nimbarte, Kishore Mullagiri, Jeshma Kovvuri and Dr. Nishant Jain

      Version of Record online: 8 APR 2014 | DOI: 10.1002/cmdc.201400069

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      Imidazzling microtubule blockers! A series of imidazo[2,1-b][1,3,4]thiadiazole-linked oxindole conjugates were synthesized and evaluated for anticancer potential. Conjugate 7 displayed promising cytotoxicity, arrested cells at the G2/M phase, and showed potent tubulin polymerization inhibition with an IC50 value of 0.15 μM.

    9. Fluorine-Containing 6,7-Dialkoxybiaryl-Based Inhibitors for Phosphodiesterase 10 A: Synthesis and in vitro Evaluation of Inhibitory Potency, Selectivity, and Metabolism (pages 1476–1487)

      Dr. Gregor Schwan, Dr. Ghadir Barbar Asskar, Dr. Norbert Höfgen, Dr. Lenka Kubicova, Dr. Uta Funke, Ute Egerland, Dr. Michael Zahn, Prof. Dr. Karen Nieber, Dr. Matthias Scheunemann, Prof. Dr. Norbert Sträter, Prof. Dr. Peter Brust and Prof. Dr. Detlef Briel

      Version of Record online: 11 APR 2014 | DOI: 10.1002/cmdc.201300522

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      Fluor your health: Phosphodiesterase 10 A (PDE10A) has emerged as an attractive target for the development of 18F-labelled brain imaging agents for positron emission tomography. A series of fluorinated dialkoxybiaryl compounds were synthesized and evaluated as PDE10A inhibitors, assisted by QSAR docking studies. The 7-fluoromethoxy derivative appears to be a promising candidate for further development.

    10. Insight into the Functional and Structural Properties of 3-Arylcoumarin as an Interesting Scaffold in Monoamine Oxidase B Inhibition (pages 1488–1500)

      Dr. Maria João Matos, Dr. Santiago Vilar, Dr. Verónica García-Morales, Dr. Nicholas P. Tatonetti, Prof. Eugenio Uriarte, Prof. Lourdes Santana and Prof. Dolores Viña

      Version of Record online: 8 APR 2014 | DOI: 10.1002/cmdc.201300533

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      Coumarins crossing the barrier: The design and synthesis of a new series of halogenated 3-arylcoumarins are described. Monoamine oxidase A and B in vitro inhibition studies, in silico prediction of passive blood–brain partitioning, and docking calculations showed most of the 3-arylcoumarin compounds to be potent and selective.

    11. Targeting Cystalysin, a Virulence Factor of Treponema denticola-Supported Periodontitis (pages 1501–1511)

      Dr. Francesca Spyrakis, Dr. Barbara Cellini, Dr. Stefano Bruno, Dr. Paolo Benedetti, Dr. Emanuele Carosati, Prof. Gabriele Cruciani, Dr. Fabrizio Micheli, Dr. Antonio Felici, Prof. Pietro Cozzini, Prof. Glen E. Kellogg, Prof. Carla Borri Voltattorni and Prof. Andrea Mozzarelli

      Version of Record online: 11 MAR 2014 | DOI: 10.1002/cmdc.201300527

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      Biting back: Cystalysin from Treponema denticola has been proposed as a potential antimicrobial target, because it is a virulence factor in adult periodontitis. Specific inhibitors of cystalysin activity were identified and assayed by complementary in silico and in vitro methods. Compounds found by these techniques might be suitable for the treatment of periodontitis after further optimization.

    12. Computational and Experimental Insight into the Molecular Mechanism of Carboxamide Inhibitors of Succinate-Ubquinone Oxidoreductase (pages 1512–1521)

      Xiao-Lei Zhu, Li Xiong, Hui Li, Xin-Ya Song, Jing-Jing Liu and Prof. Guang-Fu Yang

      Version of Record online: 12 FEB 2014 | DOI: 10.1002/cmdc.201300456

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      Antifungal mechanics: SQR is a novel target for a large family of fungicides, yet the mechanism of action remains unclear, and the bioactive conformation of the inhibitors in the SQR binding pocket has not been identified. In this study, the kinetics of SQR inhibition by ten carboxamide fungicides were measured. Along with results of modeling experiment, these findings provide valuable information for the design of more potent and specific SQR inhibitors.

    13. Anti-Dengue-Virus Activity and Structure–Activity Relationship Studies of Lycorine Derivatives (pages 1522–1533)

      Peng Wang, Lin-Feng Li, Dr. Qing-Yin Wang, Dr. Lu-Qing Shang, Dr. Pei-Yong Shi and Prof. Dr. Zheng Yin

      Version of Record online: 26 FEB 2014 | DOI: 10.1002/cmdc.201300505

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      Alkaloids that bite back: Dengue is a systemic viral infection that is transmitted to humans by Aedes mosquitoes. Currently, vaccines or specific therapeutics are not available. Lycorine, which is a natural alkaloid, has reportedly demonstrated biological activity against dengue virus (DENV). A series of lycorine derivatives and their anti-DENV activities are reported herein.

    14. 1-(1H-Indol-3-yl)ethanamine Derivatives as Potent Staphylococcus aureus NorA Efflux Pump Inhibitors (pages 1534–1545)

      Dr. Arnaud Hequet, Dr. Olga N. Burchak, Dr. Matthieu Jeanty, Dr. Xavier Guinchard, Dr. Emmanuelle Le Pihive, Dr. Laure Maigre, Pascale Bouhours, Prof. Dominique Schneider, Prof. Max Maurin, Dr. Jean-Marc Paris, Dr. Jean-Noël Denis and Prof. Dr. Claude Jolivalt

      Version of Record online: 26 MAR 2014 | DOI: 10.1002/cmdc.201400042

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      A pump turn off: 1-(1H-Indol-3-yl)ethanamine derivatives such as the one shown here, were synthesized through simple chemical modifications and were shown to be efficient NorA efflux pump inhibitors. They are able to restore ciprofloxacin activity against fluoroquinolone-resistant Staphylococcus aureus strains.

    15. Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6-Diarylpyridinamines as a Novel Class of HIV-1 NNRTIS (pages 1546–1555)

      Zhi-Yuan Wu, Na Liu, Dr. Bingjie Qin, Dr. Li Huang, Dr. Fei Yu, Dr. Keduo Qian, Dr. Susan L. Morris-Natschke, Prof. Shibo Jiang, Prof. Chin Ho Chen, Prof. Kuo-Hsiung Lee and Prof. Lan Xie

      Version of Record online: 4 JUN 2014 | DOI: 10.1002/cmdc.201400075

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      Taking the lead! Among 19 new halogenated diarylpyridinamine (DAPA) analogues, (E)-6-(2′′-bromo-4′′-cyanovinyl-6′′-methoxy)phenoxy-N2-(4′-cyanophenyl)pyridin-2,3-diamine (8 c) displays low-nanomolar antiviral potency (3–7 nM) against wild-type HIV and E138K or K101E mutant strains; it also exhibits promising drug-like properties. Compound 8 c merits development as an anti-HIV drug candidate.

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      Simplified Silvestrol Analogues with Potent Cytotoxic Activity (pages 1556–1566)

      Dr. Bill C. Hawkins, Dr. Lisa M. Lindqvist, Duong Nhu, Dr. Phillip P. Sharp, Dr. David Segal, Dr. Andrew K. Powell, Dr. Michael Campbell, Dr. Eileen Ryan, Dr. Jennifer M. Chambers, Dr. Jonathan M. White, Dr. Mark A. Rizzacasa, Dr. Guillaume Lessene, Prof. David C. S. Huang and Dr. Christopher J. Burns

      Version of Record online: 27 MAR 2014 | DOI: 10.1002/cmdc.201400024

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      Simplified complexity! The natural products silvestrol (1) and episilvestrol (2) are translation initiation inhibitors with potent anticancer activity. We report replacing the complex pseudo-sugar moiety at C6 with readily accessible and drug-like moieties. Selected compounds show potent anti-leukemic activity in vitro.

    17. Novel Heterobimetallic Radiotheranostic: Preparation, Activity, and Biodistribution (pages 1567–1573)

      Dr. Louis Adriaenssens, Dr. Qiang Liu, Dr. Fanny Chaux-Picquet, Dr. Semra Tasan, Dr. Michel Picquet, Prof. Franck Denat, Prof. Pierre Le Gendre, Dr. Fernanda Marques, Dr. Célia Fernandes, Dr. Filipa Mendes, Dr. Lurdes Gano, Dr. Maria Paula Cabral Campello and Dr. Ewen Bodio

      Version of Record online: 21 JAN 2014 | DOI: 10.1002/cmdc.201300494

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      Two metals better than one: A novel RuII(arene) theranostic complex is based on a new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo. The heteroditopic ligand can be sequentially and selectively metalated (first with Ru, then with 153Sm). The resulting heterobimetallic complex exhibits interesting cytotoxicity, water solubility, and stability. Initial biodistribution studies in healthy mice were performed as a proof of concept.

    18. Chiral Resolution and Pharmacological Characterization of the Enantiomers of the Hsp90 Inhibitor 2-Amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one Oxime (pages 1574–1585)

      Dr. Raffaella Amici, Dr. Chiara Bigogno, Dr. Roberto Boggio, Dr. Andrea Colombo, Dr. Stephen M. Courtney, Dr. Roberto Dal Zuffo, Dr. Giulio Dondio, Dr. Fulvia Fusar, Dr. Stefania Gagliardi, Prof. Dr. Saverio Minucci, Dr. Marco Molteni, Dr. Christian A. G. N. Montalbetti, Dr. Annalisa Mortoni, Dr. Mario Varasi, Dr. Stefania Vultaggio and Dr. Ciro Mercurio

      Version of Record online: 17 APR 2014 | DOI: 10.1002/cmdc.201400037

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      Problem resolved: A chemical method to resolve the enantiomers of 2-amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one oxime, a Hsp90 inhibitor targeting the N-terminal adenosine triphosphatase site, and the characterization of their inhibitor activity on Hsp90, along with the consequent antiproliferative effect on cancer cells is explored. Pharmacokinetic properties and antitumor activity are also evaluated.

    19. Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κPS-Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands (pages 1586–1593)

      Gerd Ludwig, Ivan Ranđelović, Dr. Danijela Maksimović-Ivanić, Dr. Sanja Mijatović, Mirna Z. Bulatović, Dr. Djordje Miljković, Prof. Marcus Korb, Prof. Dr. Heinrich Lang, Prof. Dr. Dirk Steinborn and Prof. Dr. Goran N. Kaluđerović

      Version of Record online: 27 JAN 2014 | DOI: 10.1002/cmdc.201300479

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      Iridium-based anticancer agents of the type [Ir(η5-C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}] (x=0–2) and [Ir(η5-C5Me5)- Cl{Ph2PCH2CH2CH2S(O)xPh-κPS}][PF6] (x=0, 1) are with high biological potential were designed, synthesized and evaluated. Their structure–activity relationships and tumoricidal action are discussed.

    20. ‘À la Carte’ Peptide Shuttles: Tools to Increase Their Passage across the Blood–Brain Barrier (pages 1594–1601)

      Dr. Morteza Malakoutikhah, Bernat Guixer, Pol Arranz-Gibert, Dr. Meritxell Teixidó and Prof. Ernest Giralt

      Version of Record online: 24 MAR 2014 | DOI: 10.1002/cmdc.201300575

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      On the menu: Flexibility, chirality, and the incorporation of halogenated amino acids are, among others, tools that can be used ‘à la carte’ to increase the passage of peptide shuttles across the blood–brain barrier (BBB). This study paves the way for a strategy in which a particular fine-tuned shuttle can be used for the transport of a given specific drug cargo.

    21. 3-Aminoazetidin-2-one Derivatives as N-Acylethanolamine Acid Amidase (NAAA) Inhibitors Suitable for Systemic Administration (pages 1602–1614)

      Dr. Annalisa Fiasella, Dr. Andrea Nuzzi, Dr. Maria Summa, Dr. Andrea Armirotti, Dr. Glauco Tarozzo, Prof. Giorgio Tarzia, Prof. Marco Mor, Dr. Fabio Bertozzi, Dr. Tiziano Bandiera and Prof. Daniele Piomelli

      Version of Record online: 14 MAY 2014 | DOI: 10.1002/cmdc.201300546

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      Stability is the key: α-Amino-β-lactams were synthesized as amide derivatives, and the effect of the azetidin-2-one ring, the stereochemistry at the α-position, and the functionalization of the α-amino group were studied with regard to N-acylethanolamine acid amidase inhibitory potency and hydrolytic and plasma stability.

  6. Retraction

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Retraction
    1. You have free access to this content
      Retracted: Synthesis and Cytotoxic Activity of 2-Anilinopyridine-3-Acrylamides as Tubulin Polymerization Inhibitors (page 1615)

      Dr. Ahmed Kamal, Md. Ashraf, M. Naseer Ahmed Khan, Vijaykumar D. Nimbarte, Shaikh Faazil, N. V. Subba Reddy and Shaik Taj

      Version of Record online: 28 MAR 2014 | DOI: 10.1002/cmdc.201400036

      This article has been retracted and is available online only.

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