Chemical Biology & Drug Design

Cover image for Vol. 82 Issue 2

August 2013

Volume 82, Issue 2

Pages i–iii, 125–241

  1. Issue Information

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

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12030

  2. Research Articles

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. Design and Synthesis of a Tetrahydroisoquinoline-Based Hydroxamate Derivative (ZYJ-34v), An Oral Active Histone Deacetylase Inhibitor with Potent Antitumor Activity (pages 125–130)

      Yingjie Zhang, Chunxi Liu, C. James Chou, Xuejian Wang, Yuping Jia and Wenfang Xu

      Version of Record online: 1 JUL 2013 | DOI: 10.1111/cbdd.12144

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      Structural modification of 1 led to another oral active HDACi 2 with simplified structure and lower molecular weight. Compared with the approved HDACi SAHA, 2 exhibited similar even superior in vitro and in vivo antitumor potency.

    2. High-throughput Screening for Identification of Inhibitors of EpCAM-Dependent Growth of Hepatocellular Carcinoma Cells (pages 131–139)

      Curtis J. Henrich, Anuradha Budhu, Zhipeng Yu, Jason R. Evans, Ekaterina I. Goncharova, Tanya T. Ransom, Xin W. Wang and James B. McMahon

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12146

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      The cancer stem cell marker, EpCAM, is an important indicator of Wnt-β-catenin signaling activation and a functional component of hepatocellular tumor initiating cells. A high-throughput screening assay idenified inhibitors of EpCAM-dependent growth of hepatocellular carcinoma cells. Several of these inhibitors were found to concomitantly inhibit expression of surface EpCAM, consisent with a requirement of EpCAM expression for continued cell growth. Further development inhibitors will provide additional insight into control of EpCAM expression and characteristics of hepatocellular cancer stem cells.

    3. Design, Synthesis, Biological Evaluation, and Docking Studies of (S)-Phenylalanine Derivatives with a 2-Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors (pages 140–146)

      Yang Liu, Yizhe Wu, Haoshu Wu, Li Tang, Peng Wu, Tao Liu and Yongzhou Hu

      Version of Record online: 28 JUN 2013 | DOI: 10.1111/cbdd.12139

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      A novel series of (S)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety were designed and synthesized. It was found that the cyclopropyl-substituted phenylalanine derivative 11h displayed the most potent DPP-4 inhibitory activity with an IC50 value of 0.247 μm. Further docking analysis of the representative compounds 11h, 11k, and 15a not only revealed the impact of binding modes on DPP-4 inhibitory activity, but also provided additional methodological values for design and optimization.

    4. Synthesis, Hypoglycaemic, Hypolipidemic and PPARγ Agonist Activities of 5-(2-Alkyl/aryl-6-Arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene-1,3-Thiazolidinediones (pages 147–155)

      Mohammed Iqbal A. Khazi, Ningaraddi S. Belavagi, Kwang R. Kim, Young-Dae Gong and Imtiyaz Ahmed M. Khazi

      Version of Record online: 1 JUL 2013 | DOI: 10.1111/cbdd.12140

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      A novel series of 5-(2-alkyl/aryl-6-arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methyllene-1,3-thiazolidinedione derivatives with one carbon atom spacer between thiazolidine-2, 4-dione moiety and fused heterocyclic ring were synthesized and characterized. These compounds were screened for hypoglycemic, hypolipidimic and PPARγ agonist activities.

    5. Synthesis, Evaluation and Molecular Docking of Prolyl-Fluoropyrrolidine Derivatives as Dipeptidyl Peptidase IV Inhibitors (pages 156–166)

      Mani Sharma, Monica Gupta, Divya Singh, Manoj Kumar and Punit Kaur

      Version of Record online: 28 JUN 2013 | DOI: 10.1111/cbdd.12142

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      A series of prolyl-fluoropyrrolidine derivatives were synthesized and evaluated for inhibition of dipeptidyl peptidase IV (DPP IV) for treatment of Type 2 diabetes. The binding position of docked compounds (stick rendering) in the binding pocket of DPP IV.

    6. Penetratin and Derivatives Acting as Antibacterial Agents (pages 167–177)

      Adriana D. Garro, Mónica S. Olivella, José A. Bombasaro, Beatriz Lima, Alejandro Tapia, Gabriela Feresin, Andras Perczel, Csaba Somlai, Botond Penke, Javier López Cascales, Ana M. Rodríguez and Ricardo D. Enriz

      Version of Record online: 1 JUL 2013 | DOI: 10.1111/cbdd.12143

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      In this study we report the synthesis, in vitro evaluation, and conformational study of penetratin and structurally related derivatives acting as antibacterial agents. Among the compounds evaluated two methionine sulfoxide derivatives (RQIKIWFQNRRM[O] KWKK-NH2 and RQIKIFFQNRRM[O]KFKK-NH2) and a nonapeptide (RQIRRWWQR-NH2) exhibited the strongest antibacterial effect against the Gram-negative and Gram-positive bacteria tested in this study.

    7. Effect of FSH Receptor-Binding Inhibitor-8 on FSH-Mediated Granulosa Cell Signaling and Proliferation (pages 178–188)

      Rajshri M. Navalakhe, Dhanashree D. Jagtap, Sumeet U. Nayak, Tarala D. Nandedkar and Smita D. Mahale

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12149

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      Effect of FSH receptor binding inhibitor-8 (FRBI-8) in FSH mediated signaling in granulosa cells is studied. FSH receptor-binding inhibitor inhibits the FSH stimulated second messenger response (cAMP and IP3) in rat granulosa cells and in further downstream events, protein kinase A expression was decreased. FSH receptor-binding inhibitor-8 affects cell proliferation in COV434 cells by arresting cell cycle progression and inducing apoptosis. Application of FRBI-8 as an antagonist of ovarian function needs to be explored.

    8. Physicochemical and Biological Characterization of Pep-1/Elastin Complexes (pages 189–195)

      Saman Ahmad Nasrollahi, Changiz Taghibiglou, Shamileh Fouladdel, Rasoul Dinarvand, Ali A. Moosavi Movahedi, Ebrahim Azizi and Effat S. Farboud

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12150

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      Our results reveal that Pep-1/elastin complex in appropriate ratio can not only transduce into cultured cells but also penetrate the living animal cells, that introducing high efficiency and effectiveness of cell-penetrating peptide/protein complexes.

    9. Insulinotropic Actions of the Frog Skin Host-Defense Peptide Alyteserin-2a: A Structure–Activity Study (pages 196–204)

      Opeolu O. Ojo, Yasser H. A. Abdel-Wahab, Peter R. Flatt and J. Michael Conlon

      Version of Record online: 28 JUN 2013 | DOI: 10.1111/cbdd.12151

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      XThe [G11K], [S7k], [S7k,G11k], and [G11k,N15K] analogs of alyteserin-2a stimulated insulin release from BRIN-BD11 clonal β-cells at 0.01 nM. Membrane depolarization and an increase in intracellular Ca2+ concentration are involved in the mechanism of action of the peptides. [G11k]alyteserin-2a (75 nmol/kg body weight) significantly (p < 0.01) enhanced insulin release and improved glucose tolerance following an intraperitoneal glucose load in high fat-fed mice with obesity and insulin-resistance.

    10. Identification of Novel Gyrase B Inhibitors as Potential Anti-TB drugs: Homology Modelling, Hybrid Virtual Screening and Molecular Dynamics Simulations (pages 205–215)

      Yushir Maharaj and Mahmoud E. S. Soliman

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12152

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      Herewith, we report an integrated multi in silico approach involving virtual screening, molecular dynamics simulations and per-residue energy analysis to discover novel anti-TB drugs.

    11. Praziquantel Derivatives with Antischistosomal Activity: Aromatic Ring Modification (pages 216–225)

      Zhi-xia Wang, Jing-lei Chen and Chunhua Qiao

      Version of Record online: 28 JUN 2013 | DOI: 10.1111/cbdd.12153

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      A series of aromatic ring modified praziquantel (PZQ) derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin.

  3. Research Letters

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. Design, Synthesis, and Biological Evaluation of Catecholamine Vehicle for Studying Dopaminergic System (pages 226–232)

      Pooja Singh, Vikas Kumar, Swati Aggarwal, Anjani K. Tiwari, Krishna Chuttani, Ramendra Pratap and Anil K. Mishra

      Version of Record online: 23 JUL 2013 | DOI: 10.1111/cbdd.12147

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      EDTA(TA)2 is evaluated neuro-optical imaging agent for dopaminergic function by fluorescence spectroscopy. The ligand-HSA interaction sites and binding constant were also identified by docking and fluorescence spectroscopy for its efficacy as neuro-agent.

    2. Discovery of a New Bioactive Molecule for Neuroblastoma (pages 233–241)

      Andrei Leitão, Alexander Schramm and Angelika Eggert

      Version of Record online: 1 JUL 2013 | DOI: 10.1111/cbdd.12148

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      A novel chemotype of an anti-neuroblastoma molecule was discovered using in silico models and cell-based assays. Our assays showed that this molecule presented a different biological profile from lestaurtinib, mainly because of its resilience for TrkB expressing cells that mimics the aggressive form of the disease in vitro. This compound opens up a new road toward an improved therapeutic possibility for this deadly disease.