Chemical Biology & Drug Design

Cover image for Vol. 83 Issue 2

February 2014

Volume 83, Issue 2

Pages i–iii, 141–258

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. Research Article
    4. Research Letter
    5. Research Articles
    1. Issue Information (pages i–iii)

      Version of Record online: 17 JAN 2014 | DOI: 10.1111/cbdd.12213

  2. Research Article

    1. Top of page
    2. Issue Information
    3. Research Article
    4. Research Letter
    5. Research Articles
    1. Crystallographic Fragment-Based Drug Discovery: Use of a Brominated Fragment Library Targeting HIV Protease (pages 141–148)

      Theresa Tiefenbrunn, Stefano Forli, Meaghan Happer, Ana Gonzalez, Yingssu Tsai, Michael Soltis, John H. Elder, Arthur J. Olson and Charles D. Stout

      Version of Record online: 30 OCT 2013 | DOI: 10.1111/cbdd.12227

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      X-marks the spot: Weak fragment binding at surface sites is more easily detected in X-ray structures when a halogen atom in the fragment can be localized via an anomalous difference peak. A brominated fragment library elucidates known surface binding sites on HIV-1 protease.

  3. Research Letter

    1. Top of page
    2. Issue Information
    3. Research Article
    4. Research Letter
    5. Research Articles
    1. 1-Thia-4,7-diaza-spiro[4.4]nonane-3,6-dione: A Structural Motif for 5-hydroxytryptamine 6 Receptor Antagonism (pages 149–153)

      Greg Hostetler, Derek Dunn, Beth A. McKenna, Karla Kopec and Sankar Chatterjee

      Version of Record online: 26 DEC 2013 | DOI: 10.1111/cbdd.12240

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      Based on “HTS-hit” compound 1a (Ki=5.73uM against h5-HT6),compound 8a (Ki=26nM) was developed. Enantiomers (Ki of 15nM vs,855nM)displayed effect of chirality on activity.

  4. Research Articles

    1. Top of page
    2. Issue Information
    3. Research Article
    4. Research Letter
    5. Research Articles
    1. Discovery of HIV-1 Integrase Inhibitors: Pharmacophore Mapping, Virtual Screening, Molecular Docking, Synthesis, and Biological Evaluation (pages 154–166)

      Hardik Bhatt, Paresh Patel and Christophe Pannecouque

      Version of Record online: 4 OCT 2013 | DOI: 10.1111/cbdd.12207

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      Computer-aided drug design approaches like pharmacophore mapping, virtual screening, and molecular docking were used to design novel compounds bearing pteridine ring system. Designed compounds were synthesized by conventional and microwave-irradiated methods showing advantage of MWI method. All synthesized compounds were evaluated as HTV-1 integrase inhibitors and further explored to discover novel HIV-I integrase inhibitors.

    2. X-ray Crystallographic and Fluorometric Analysis of the Interactions of Rhein to Human Serum Albumin (pages 167–173)

      Mei Li, Philbert Lee, Yao Zhang, ZhiYuan Ma, Feng Yang, ZuPing Zhou, XiaoYang Wu and Hong Liang

      Version of Record online: 4 OCT 2013 | DOI: 10.1111/cbdd.12208

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      The model on the interactions of complicated natural drug with HSA was built by fluorescence spectroscopy and X-ray crystallography. The binding mechanism and behavior of Rhein to HSA were analyzed and determined. The results will provide guidance for future development of rhein-based compound and a drug-HSA delivery system.

    3. Screening of Drug Target Proteins by 2D Ligand Matching Approach (pages 174–182)

      Jianyu Feng, Hong Guo, Jian Wang and Tun Lu

      Version of Record online: 5 OCT 2013 | DOI: 10.1111/cbdd.12209

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      The query drug structure is compared with all ligands in the database to obtain similar scores. Ligands with similar sores greater than a certain threshold were flagged. The procedure of potential target protein screening is shown by using DB04017 as example. Protein clusters associating with these ligands would be considered as potential targets of the query drug.

    4. Synthesis, In Vitro Cytotoxicity and Radiosensitizing Activity of Novel 3-[(2,4-Dinitrophenylamino)Alkyl] Derivatives of 5-Fluorouracil (pages 183–190)

      Ali Khalaj, Khosrou Abdi, Seyed Nasser Ostad, Mohammad Reza Khoshayand, Navid Lamei and Hasan Ali Nedaie

      Version of Record online: 4 OCT 2013 | DOI: 10.1111/cbdd.12211

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      Several novel 3[3-(2,4-dinitro-phenylamino)-alkyl]-5-fluorouracil resulting from linkage of 2,4-dinitrophenylamine through 1-6 methylene units with 5-fluorouracil were prepared and tested for in vitro cytotoxicity in HT-29 cell line under aerobic and hypoxic conditions with and without radiation. These compounds induced time- and concentration-dependent cytotoxicity which were higher under hypoxic than aerobic conditions, and showed selective radiosensitizing activities under hypoxic conditions.

    5. 4-Aminoquinoline-β-Lactam Conjugates: Synthesis, Antimalarial, and Antitubercular Evaluation (pages 191–197)

      Raghu Raj, Christophe Biot, Séverine Carrère-Kremer, Laurent Kremer, Yann Guérardel, Jiri Gut, Philip J. Rosenthal and Vipan Kumar

      Version of Record online: 28 OCT 2013 | DOI: 10.1111/cbdd.12225

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      Thirty four 4-aminoquinoline-β-lactam conjugates have been synthesized and evaluated for their antimalarial and anti-TB profiles.

    6. Synthesis and Evaluation of Chalcone Derivatives as Inhibitors of Neutrophils' Chemotaxis, Phagocytosis and Production of Reactive Oxygen Species (pages 198–206)

      Syed N. A. Bukhari, Yasmin Tajuddin, Vannessa J. Benedict, Kok W. Lam, Ibrahim Jantan, Juriyati Jalil and Malina Jasamai

      Version of Record online: 28 OCT 2013 | DOI: 10.1111/cbdd.12226

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      Chalcone derivatives were synthesised and evaluated for their inhibitory effects on PMNs chemotaxis, phagocytosis and intracellular and extracellular ROS productions. It was observed that phenyl-4-methylaminoethanol and dimethoxy substituents contributed to these effects‥

    7. Exploring the Ligand Recognition Properties of the Human Vasopressin V1a Receptor Using QSAR and Molecular Modeling Studies (pages 207–223)

      Martha C. Contreras-Romo, Marlet Martínez-Archundia, Omar Deeb, Magdalena J. Ślusarz, Gema Ramírez-Salinas, Ramón Garduño-Juárez, Andrés Quintanar-Stephano, Guillermo Ramírez-Galicia and José Correa-Basurto

      Version of Record online: 26 DEC 2013 | DOI: 10.1111/cbdd.12229

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      Exploration of V1aR under theoretical studies (MD simulations, QSAR and docking studies) to depict the principal recognition properties which could be use for drug design.

    8. Synthesis and Antimycobacterial Activity of Novel Thiadiazolylhydrazones of 1-Substituted Indole-3-carboxaldehydes (pages 224–236)

      Kamaleddin Haj Mohammad Ebrahim Tehrani, Vida Mashayekhi, Parisa Azerang, Soroush Sardari, Farzad Kobarfard and Kobra Rostamizadeh

      Version of Record online: 30 OCT 2013 | DOI: 10.1111/cbdd.12230

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      A series of indole-based thiadiazole derivatives with various substitutions at N-1 position of indole ring have been synthesized and tested for their antimycobacterial activity. Compounds 4e (R = butyl), 4f (R = pentyl), 4n (= 4-fluorobenzyl), 4p (= 4-chlorobenzyl), 4q (R = 4-bromobenzyl) and 4t (R = 4-methoxybenzyl) were the most potent derivatives with IC50 value of 3.91 µg/mL.

    9. Mapping of Allosteric Druggable Sites in Activation-Associated Conformers of the M2 Muscarinic Receptor (pages 237–246)

      Yinglong Miao, Sara E. Nichols and J. Andrew McCammon

      Version of Record online: 30 OCT 2013 | DOI: 10.1111/cbdd.12233

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      FTMAP is applied to search for allosteric druggable sites in the activation-associated conformers of the M2 muscarinic receptor that were revealed from accelerated molecular dynamics simulation. Seven allosteric sites are identified in the M2 receptor and they are distributed in the solvent-exposed extracellular and intracellular mouth regions, as well as the lipid-exposed pockets formed by the transmembrane α helices TM3-TM4, TM5-TM6 and TM7-TM1/TM2. These sites may serve as promising target sites for designing novel allosteric modulators as receptor-selective drugs.

    10. Discovering Isozyme-Selective Inhibitor Scaffolds of Human Carbonic Anhydrases Using Structural Alignment and De novo Drug Design Approaches (pages 247–258)

      Fu Xiang, Jun Xiang, Yuanping Fang, Mingju Zhang and Maoteng Li

      Version of Record online: 26 DEC 2013 | DOI: 10.1111/cbdd.12234

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      To make the spatial structures of complexes comparable, the coordinates for CA domains were reassigned based on structural alignments. The preferred docking poses of SBR in CAs, p17, were reduced to the form H*-SO2NH2, i.e. seed structure, fragments will be added to the growing site to generate new molecules. The results suggested that sulfonamide derivatives with naphthalene, fluorene, and acridan as the scaffold structures can be the potential isozyme-selective CAIs, especially for isozymes CA II, IV, and IX.

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