Chemical Biology & Drug Design

Cover image for Vol. 83 Issue 1

January 2014

Volume 83, Issue 1

Pages i–iii, 1–140

  1. Issue Information

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

      Article first published online: 23 DEC 2013 | DOI: 10.1111/cbdd.12212

  2. Review

    1. Top of page
    2. Issue Information
    3. Review
    4. Research Articles
    5. Research Letter
    6. Research Articles
    7. Research Letters
    1. Potassium Channels: Structures, Diseases, and Modulators (pages 1–26)

      Chuan Tian, Ruixin Zhu, Lixin Zhu, Tianyi Qiu, Zhiwei Cao and Tingguo Kang

      Article first published online: 23 DEC 2013 | DOI: 10.1111/cbdd.12237

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      Three aspects including structures, diseases and modulators are mainly discussed in this review. The latest developments in structure determinants and regulation mechanism of all types of potassium channels are summarized. Diseases related to potassium channels are reviewed. Both qualitative and quantitative analyses are made on modulators. All these studies on potassium channels as possible pharmaceutical targets will facilitate translational research in the future.

  3. Research Articles

    1. Top of page
    2. Issue Information
    3. Review
    4. Research Articles
    5. Research Letter
    6. Research Articles
    7. Research Letters
    1. Identification of Type II Inhibitors Targeting BRAF Using Privileged Pharmacophores (pages 27–36)

      Qingwen Zhang, Juan Wang, Fei Wang, Xiuhua Chen, Yunsong He, Qidong You and Houyuan Zhou

      Article first published online: 25 OCT 2013 | DOI: 10.1111/cbdd.12198

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      A novel pharmacophore, 4-phenylaminopyrimidine urea (4-PAPU) was hybrid-designed to successfully identify selective inhibitors of BRAF. Docking suggested that they might be type II kinase inhibitors binding to the DFG-out conformation of BRAF.

    2. Optimization of Compound Ranking for Structure-Based Virtual Ligand Screening Using an Established FRED–Surflex Consensus Approach (pages 37–51)

      Jiangfeng Du, Ivo W. M. Bleylevens, Albert V. Bitorina, Kanin Wichapong and Gerry A. F. Nicolaes

      Article first published online: 4 OCT 2013 | DOI: 10.1111/cbdd.12202

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      A systematic study into the optimal combination of ranked score lists from ensemble docking when applied to a hierarchic docking protocol that combines rigid and flexible docking with FRED and Surflex, respectively, is presented. The results provide information and guidelines on how to optimally perform such hierarchic ensemble docking for use in structure-based virtual screening.

  4. Research Letter

    1. Top of page
    2. Issue Information
    3. Review
    4. Research Articles
    5. Research Letter
    6. Research Articles
    7. Research Letters
    1. Synthetic Substrates Specific to Activated Plasmin Can Monitor the Enzymatic Functional Status in Situ in Breast Cancer Cells (pages 52–57)

      Keigo Gohda, Ko Fujimori, Naoki Teno, Keiko Wanaka and Yuko Tsuda

      Article first published online: 30 OCT 2013 | DOI: 10.1111/cbdd.12232

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      We designed synthetic substrates specific to target molecules to directly estimate enzymatic functionality in situ. It contains a probing unit, an organic fragment specific for enzyme-binding; and a reactive unit, a natural peptide subject to catalysis. In this study, activation of plasminogen to plasmin was examined in MDA-MB231 breast cancer cells, and the localization and function of plasmin were successfully visualized by fluorophore in the substrate. This would be the first time for activated plasmin at work in situ by direct observation.

  5. Research Articles

    1. Top of page
    2. Issue Information
    3. Review
    4. Research Articles
    5. Research Letter
    6. Research Articles
    7. Research Letters
    1. Synthesis, Characterization, and Biological Evaluation of 99mTc(CO)3-Labeled Peptides for Potential Use as Tumor Targeted Radiopharmaceuticals (pages 58–70)

      Rinku Baishya, Dipak K. Nayak, Nabanita Chatterjee, Kamal K. Halder, Sanmoy Karmakar and Mita C. Debnath

      Article first published online: 1 NOV 2013 | DOI: 10.1111/cbdd.12166

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      Three linear peptides were synthesised by changing the amino acid sequence of RGD motif and radiolabeled with freshly prepared [99mTc(CO)3(H2O)3]+ precursor (yield ~ 97%). Radiolabeled peptides were substantially stable up to 24 h when incubated with saline, serum and histidine solution (10−2 m), also exhibited significant and rapid internalization in both EAC and αvβ3-positive B16F10 mouse melanoma cell line. Fast blood clearance, rapid urinary excretion and significantly high tumor to muscle ratios are encouraging enough to carry out further experiments for targeting tumor.

    2. Comparative Kinetics of Qi Site Inhibitors of Cytochrome bc1 Complex: Picomolar Antimycin and Micromolar Cyazofamid (pages 71–80)

      Hui Li, Xiao-Lei Zhu, Wen-Chao Yang and Guang-Fu Yang

      Article first published online: 19 SEP 2013 | DOI: 10.1111/cbdd.12199

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      In this paper, a comparative investigation of the inhibitory kinetics of antimycin and cyazofamid against the porcine bc1 complex was performed. The resulsts show that antimycin was a slow tight-binding inhibitor and cyazofamid was a typical classical inhibitor. Combined with molecular docking and quantum mechanics calculations, the detailed mechanism of inhibition by Qi inhibitors was obtained.

    3. Structural Bioinformatics-Based Identification of EGFR Inhibitor Gefitinib as a Putative Lead Compound for BACE (pages 81–88)

      Mingshan Niu, Jin Hu, Sijin Wu, Xiaoe Zhang, Huaxi Xu, Yunwu Zhang, Jie Zhang and Yongliang Yang

      Article first published online: 4 OCT 2013 | DOI: 10.1111/cbdd.12200

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      Structural-bioinformatics approach has been rather successful to predict off-target binding and guide polypharmacological drug design. Herein we describe the identification of Gefitinib as a potential lead compound for BACE.

    4. Combined 3D-QSAR, Molecular Docking, Molecular Dynamics Simulation, and Binding Free Energy Calculation Studies on the 5-Hydroxy-2H-Pyridazin-3-One Derivatives as HCV NS5B Polymerase Inhibitors (pages 89–105)

      Haijing Yu, Yu Fang, Xia Lu, Yongjuan Liu and Huabei Zhang

      Article first published online: 4 OCT 2013 | DOI: 10.1111/cbdd.12203

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      The NS5B polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus drugs. In this work, a combined molecular modeling study, including 3D-QSAR, molecular docking, MD simulation (40 ns, using ten compounds with diverse structures and activities), and binding free energy calculation, was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The results from this study can provide some insights into the development of novel potent NS5B inhibitors.

    5. Structure–Activity Relationships of New 1-substitutedmethyl-4-[5-(N-methyl-N-propylamino)pentyloxy]piperidines and Selected 1-[(N-substituted-N-methyl)-3-propyloxy]-5-(N-methy-l-N-propyl)-pentanediamines as H3-Antagonists (pages 106–118)

      Iwona Masłowska-Lipowicz and Krzysztof Walczyński

      Article first published online: 28 OCT 2013 | DOI: 10.1111/cbdd.12206

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      The present compounds contain a 4-hydroxypiperidine core, which behaves as a conformationally restricted version of the 3-amino-1-propanol moiety common to the many previously described non-imidazole H3 ligands. Detailed structure-activity studies revealed that 1-(2-benzofuranylmethyl)- 5c (pA2 = 8.47 ± 0.05) and 1-(3-benzofuranylmethyl)-4-[5-(N-methyl-N-propyl)pentyloxy]piperidine 5d (pA2 = 8.15 ± 0.07) exhibit high potency for the H3 histamine receptor. Replacement of the 4-hydroxypiperidine of the leads 7 and 5c by a highly flexible 3-(methylamino)propyloxy chain yields compounds 6a (pA2 = 8.02) and 6b (pA2 = 6.23) with higher and lower potency than their piperidine analogues (7, pA2 = 7.79; 5c, pA2 = 8.47), respectively.

    6. Antioxidant, α-Glucosidase and Xanthine Oxidase Inhibitory Activity of Bioactive Compounds From Maize (Zea mays L.) (pages 119–125)

      Shivraj H. Nile and Se W. Park

      Article first published online: 4 OCT 2013 | DOI: 10.1111/cbdd.12205

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      Chemical investigations of maize kernels yielded ten phenolic compounds which were structurally established using chromatographic and spectroscopic analysis. The isolated phenolics (M1M10) were studied for antioxidant abilities by DPPH radical scavenging activity, reducing ability, and OH radical scavenging activity, with α-glucosidase and xanthine oxidase inhibition. The isolated maize phenolics revealed potent xanthine oxidase and α-glucosidase inhibitory activity to that of allopurinaol and acarbose in vitro and in vivo, respectively. The kinetics study with xanthine oxidase reveled competitive type of inhibition to vanillic acid (M2), ferulic acid (M5), 3′-methoxyhirsutrin (M7), and peonidin-3-glucoside (M10) isolated compounds from maize as compared to control allopurinol. Overall, with few exceptions, all the phenolic compounds from maize kernel showed significant biological activities with all parameters examined in this study.

  6. Research Letters

    1. Top of page
    2. Issue Information
    3. Review
    4. Research Articles
    5. Research Letter
    6. Research Articles
    7. Research Letters
    1. Mefloquine–Oxazolidine Derivatives: A New Class of Anticancer Agents (pages 126–131)

      Felipe A. R. Rodrigues, Igor da S. Bomfim, Bruno C. Cavalcanti, Claudia Pessoa, Raoni S. B. Goncalves, James L. Wardell, Solange M. S. V. Wardell and Marcus V. N. de Souza

      Article first published online: 5 OCT 2013 | DOI: 10.1111/cbdd.12210

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      A series of twenty three racemic mefloquine-oxazolidine derivatives have been evaluated for their activity against 3–5 cancer cell lines SF–295, HCT–116, OVCAR–8, HCT–8 and HL–60. Cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 µg/mL.

    2. Characteristic Structural Features of Indolicidin: Effects of the cis-trans Isomerism on its Conformation (pages 132–140)

      Balázs Leitgeb

      Article first published online: 23 DEC 2013 | DOI: 10.1111/cbdd.12238

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      Structural features of eight different stereoisomeric forms of antimicrobial peptide, indolicidin were identified, as well as the effects of cis-trans isomerism on the conformation of indolicidin were investigated. The results obtained by the molecular dynamics simulations pointed out that the distinct stereoisomers of indolicidin adopted typical conformational properties, regarding their secondary structures and intramolecular interactions. Additionally, it could be concluded that the appearance of turn structures and intramolecular interplays depended on the cis or trans nature of Xaa-Pro peptide bonds.

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