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April 15, 2014

VIP: High-Throughput Screening of Metal–N-Heterocyclic Carbene Complexes against Biofilm Formation by Pathogenic Bacteria

VIP: High-Throughput Screening of Metal–N-Heterocyclic Carbene Complexes against Biofilm Formation by Pathogenic BacteriaThierry Bernardi,* Stéphanie Badel, Pascal Mayer, Jérome Groelly, Pierre de Frémont, Béatrice Jacques, Pierre Braunstein, Marie-Laure Teyssot, Christelle Gaulier, Federico Cisnetti, Arnaud Gautier,* Sylvain Roland*

The treatment of certain bacterial infections has become a major public health concern with the increasing emergence of pathogenic bacterial strains that are resistant to most available antibiotics. Alternative strategies to those involving conventional antibiotic treatments are urgently needed to treat these refractory infections. Read more...

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  1. Getting to the Source: Selective Drug Targeting of Cancer Stem Cells

    Fatima Ismail and Prof. David A. Winkler

    Article first published online: 23 APR 2014 | DOI: 10.1002/cmdc.201400068

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    Getting to the source of cancer: The cancer stem cell hypothesis states that some tumor cells have stem-cell-like properties and consequently are typically not reached by traditional chemotherapy, causing patients to relapse after periods of remission. As such, cancer stem cells represent a novel target for the development of more efficacious drugs. Here, recent advances in the development of small molecules targeting cancer stem cells are reviewed.

  2. Photodelivery of CO by Designed PhotoCORMs: Correlation between Absorption in the Visible Region and Metal–CO Bond Labilization in Carbonyl Complexes

    Dr. Indranil Chakraborty, Samantha J. Carrington and Prof. Pradip K. Mascharak

    Article first published online: 23 APR 2014 | DOI: 10.1002/cmdc.201402007

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    Break it up! Despite strong absorptions in the visible range, [MnBr(azpy)(CO)3] and [ReBr(azpy)(CO)3], two structurally and electronically similar metal–carbonyl complexes, exhibit very different CO photolability upon exposure to visible light. Our theoretical study results that explain these differences may be useful to future studies of photoactive CO-donating drugs triggered by visible/near-IR light.

  3. Insight into the Recognition, Binding, and Reactivity of Catalytic Metallodrugs Targeting Stem Loop IIb of Hepatitis C IRES RNA

    Seth S. Bradford, Martin James Ross, Insiya Fidai and Dr. J. A. Cowan

    Article first published online: 22 APR 2014 | DOI: 10.1002/cmdc.201400070

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    Metal with mettle: Catalytic metallodrugs are a new compound class with potential for high therapeutic activity and low toxicity. The Cu-GGHYrFK-amide complex was reported earlier to catalytically inactivate stem loop IIb of the HCV internal ribosomal entry site RNA, and to show significant antiviral activity in a cellular HCV replicon assay. Herein we describe our studies focused on understanding the cleavage mechanism and the relationship of catalyst configuration to structural recognition and site-selective cleavage of the structured RNA motif.

  4. Photoinduced Intercalation and Coordination of a Dirhodium Complex to DNA: Dual DNA Binding

    Alycia M. Palmer, Scott J. Burya, Judith C. Gallucci and Prof. Claudia Turro

    Article first published online: 17 APR 2014 | DOI: 10.1002/cmdc.201402004

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    Dual impact with light:­ cis-H,H-[Rh2(OCCH3NH)2(dppz)(CH3CN)4]2+ exhibits enhanced intercalation and covalent binding to DNA upon activation with visible light. The unique photoinduced dual binding of this complex makes it an attractive photodynamic therapy agent, which may be active against cisplatin-resistant cell lines.

  5. 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

    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

    Article first published 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.