Chemical Biology & Drug Design

Cover image for Vol. 83 Issue 4

April 2014

Volume 83, Issue 4

Pages i–iii, 379–506

  1. Issue Information

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

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12215

  2. Research Articles

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. Quantitative Sequence–Activity Model Analysis of Oligopeptides Coupling an Improved High-Dimension Feature Selection Method with Support Vector Regression (pages 379–391)

      Lifeng Wang, Zhijun Dai, Hongyan Zhang, Lianyang Bai and Zheming Yuan

      Article first published online: 18 FEB 2014 | DOI: 10.1111/cbdd.12242

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      This paper used 531 physicochemical property parameters to characterize oligopeptides, and then a rapid selection method BMRF was proposed to nonlinearly select the high-dimensional features. Based on reserved features, a novel model was constructed for QSAM analysis of two oligopeptide systems, which shows a significant improvement in modeling performance especially in external prediction. And also, the real biochemical significance corresponding to reserved descriptors can be given directly through improved interpretation system.

    2. Design, Synthesis and Bioevaluation of Novel N-Substituted-3,5-Bis(Arylidene)-4-piperidone Derivatives as Cytotoxic and Antitumor Agents with Fluorescent Properties (pages 392–400)

      Jufeng Sun, Shuping Zhang, Chen Yu, Guige Hou, Xiaofan Zhang, Keke Li and Feng Zhao

      Article first published online: 1 FEB 2014 | DOI: 10.1111/cbdd.12254

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      Ten new N-substituted-3,5-bis(http://www.iciba.com/benzylidene)-4-piperidones were synthesized and reported. Their antitumor activities were screened against human carcinoma cell lines SW1990, MIA PaCa-2, PG-BE1, NCI-H460 and SK-BR-3 by a CCK-8 method. In addition, their interesting fluorescent properties were investigated. The results demonstrated these molecules deserve further research to improve potencies as useful templates and possess high potential as promising fluorescent antitumor agents.

    3. Beyond Topoisomerase Inhibition: Antitumor 1,4-Naphthoquinones as Potential Inhibitors of Human Monoamine Oxidase (pages 401–410)

      Eduardo Coelho-Cerqueira, Paulo A. Netz, Vanessa P. do Canto, Angelo C. Pinto and Cristian Follmer

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12255

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      Antitumor spermidine-1,4-naphthoquinones are reversible and competitive MAO inhibitors. Spermidine-1,4-NQs that act as potent inhibitors of MAO are capable of binding to FAD moiety. The application of spermidine-1,4-naphthoquinones in cancer therapy should consider their effect on MAO activity.

    4. Purification and Modeling Amphipathic Alpha Helical Antimicrobial Peptides from Skin Secretions of Euphlyctis cyanophlyctis (pages 411–417)

      Ahmad Asoodeh, Samaneh Sepahi and Adel Ghorani-Azam

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12256

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      Two new antimicrobial peptides from skin secretions of Euphlyctis cyanophlyctis were purified and their antibacterial activities and minimum inhibitory concentration (MIC) were evaluated. Hemolysis assay was used to examine their nontoxic effects on human red blood cells (RBCs). Structural prediction, suggested that the extracted peptides can efficiently bind to cell membrane or bind to targets inside the cells.

    5. Effect of Chain Elongation on Biological Properties of the Toxin Paralysin β-Alanyl-tyrosine (pages 418–426)

      Anna Macurkova, Tereza Neubauerova, Kristyna Poncova, Rudolf Jezek, Petra Lovecka, Vojtech Spiwok, Martina Mackova and Tomas Macek

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12257

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      The extension of the simple chain of β-alanyl-tyrosine stabilizes the structure to form doublehelix-like conformation, improves the anti-microbial properties while revealing no significant effect on its haemolytic activity or toxic action against mammalian cells.

    6. Discovery of New Sites for Drug Binding to the Hypertension-Related Renin–Angiotensinogen Complex (pages 427–439)

      Natércia F. Brás, Pedro A. Fernandes and Maria J. Ramos

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12258

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      The aspartic protease renin (REN) is a crucial enzyme for the control of blood pressure and thus a major target for drug design studies, but very few strategies have proved successful so far. In this work, a computational alanine scanning mutagenesis (ASM) method was used to get a broad picture of all protein–protein interactions established between this enzyme and its substrate during the steps that lead to proteolytic catalysis. We identified the residues that contribute the most to the establishment of a stable binding interface, which should prove excellent targets to the development of drugs able to prevent or disrupt this interaction. This study is of interest for the pharmaceutical industry, and all the computational mutagenesis insights will help guide future studies in developing strategies for renin inactivation.

    7. High-Throughput Screen of Natural Product Extracts in A Yeast Model of Polyglutamine Proteotoxicity (pages 440–449)

      Gladis M. Walter, Avi Raveh, Sue-Ann Mok, Thomas J. McQuade, Carl J. Arevang, Pamela J. Schultz, Matthew C. Smith, Samuel Asare, Patricia G. Cruz, Susanne Wisen, Teatulohi Matainaho, David H. Sherman and Jason E. Gestwicki

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12259

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      A ‘live-dead’ assay for polyQ toxicity was developed and miniaturized for 384-well format. Activators of a stress response were identified as anti-polyQ compounds by screening a pre-fractionated natural product collection.

    8. You have full text access to this OnlineOpen article
      Two- and Three-dimensional Rings in Drugs (pages 450–461)

      Matteo Aldeghi, Shipra Malhotra, David L. Selwood and Ah Wing Edith Chan

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12260

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      A detailed analysis of 3D and 2D ring fragments in marketed drugs is presented, taking also into account the protein classes targeted by each ring fragment. The high structural and shape diversity of 3D ring systems appears to be important in bioactive compounds targeting specific targets classes.

    9. Molecular Modeling of 5HT2A Receptor – Arylpiperazine Ligands Interactions (pages 462–471)

      Milan Sencanski, Vladimir Sukalovic, Kaveh Shakib, Vukic Soskic, Ljiljana Dosen-Micovic and Sladjana Kostic-Rajacic

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12261

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      The 5HT2A receptor model was built using available coordinates of human β2 adrenergic receptor as a template. The proposed model was subjected to explicit membrane simulations, in order to relax the obtained protein conformation and to prove its stability. Different arylpiperazines were further docked in order to determine receptor-ligand interactions. To validate the obtained model a custom binary database of 40 compounds was used.

    10. The Impact of Active Site Mutations of South African HIV PR on Drug Resistance: Insight from Molecular Dynamics Simulations, Binding Free Energy and Per-Residue Footprints (pages 472–481)

      Shaimaa M. Ahmed, Glenn E. M. Maguire, Hendrik G. Kruger and Thirumala Govender

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12262

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      Molecular dynamics and binding free energy calculations showed that the binding affinity of inhibitors for the V82F/I84V double mutant is impaired significantly compared with wild type and V82A mutant. It was found that localized mutations can disturb the binding affinity of the inhibitors toward the nearby, and some cases distant, residues. Entropic loss was found to play a role in binding affinity with some inhibitors more than the others.

    11. 4-Hydroxy-α-Tetralone and its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant Escherichia coli (pages 482–492)

      Gaurav R. Dwivedi, Harish C. Upadhyay, Dharmendra K. Yadav, Vigyasa Singh, Santosh K. Srivastava, Feroz Khan, Nandan S. Darmwal and Mahendra P. Darokar

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12263

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      Drug resistance reversal potential and mechanism of natural compound 1 4-hydroxy-α-tetralone and its derivative 1e 3,4,5-trimethoxy benzoyl were deduced through inhibition of ATP dependent efflux pumps. Inhibition of efflux pumps is useful in: (i) lowering the dose of antibiotics; (ii) reducing the drug resistance development frequency; and (iii) increasing the efficacy of antibiotics against multidrug resistant Escherichia coli strains.

  3. Research Letters

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. Immunostimulatory Lipid Nanoparticles from Herbal Medicine (pages 493–497)

      Tal H. Hasson, Anna Takaoka, Roberto de la Rica, Hiroshi Matsui, Gabriela Smeureanu, Charles M. Drain and Akira Kawamura

      Article first published online: 5 FEB 2014 | DOI: 10.1111/cbdd.12250

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      Immunostimulatory glycolipids from herbal medicine form nanoparticles in a solvent-dependent manner. While larger nanoparticles of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles of the same lipids exhibited substantially higher potency. The result points to a possibility that similar nanoassemblies are playing important roles in the biological activities of many organic molecules and drugs.

    2. Discovery and Structure Optimization of a Series of Isatin Derivatives as Mycobacterium tuberculosis Chorismate Mutase Inhibitors (pages 498–506)

      Variam U. Jeankumar, Reshma Alokam, Jonnalagadda P. Sridevi, Priyanka Suryadevara, Siddharth S. Matikonda, Santosh Peddi, Seedarala Sahithi, Mallika Alvala, Perumal Yogeeswari and Dharmarajan Sriram

      Article first published online: 18 MAR 2014 | DOI: 10.1111/cbdd.12265

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      2D interaction profile of compounds 1, 7 and 25 with the active site residues.

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