Chemical Biology & Drug Design

Cover image for Chemical Biology & Drug Design

February 2013

Volume 81, Issue 2

Pages i–iii, 167–309

  1. Issue Information

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

      Version of Record online: 10 JAN 2013 | DOI: 10.1111/cbdd.12024

  2. Research Articles

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letter
    1. Alanine Scan of an Immunosuppressive Peptide (CP): Analysis of Structure–Function Relationships (pages 167–174)

      Laura Raguine, Marina Ali, Veronika Bender, Eve Diefenbach, Munikumar Reddy Doddareddy, David Hibbs and Nicholas Manolios

      Version of Record online: 26 NOV 2012 | DOI: 10.1111/cbdd.12080

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      Core Peptide (CP) is an immunosuppressive peptide, the sequence of which is derived from the T-cell antigen receptor alpha chain transmembrane region. Here we report the role each constituent amino acid plays within CP using an alanine scan and the amino acid effect on function using a biological antigen presentation assay. We have now identified that there are four hydrophobic regions and one positively charged region within CP necessary for biological activity.

    2. Identification of Novel Anaplastic Lymphoma Kinase (ALK) Inhibitors Using a Common Feature Pharmacophore Model Derived from Known Ligands Crystallized with ALK (pages 175–184)

      Huan-Zhang Xie, Hai Lan, You-Li Pan, Jun Zou, Ze-Rong Wang, Lin-Li Li, Qi Huang, Hui Zhang and Sheng-Yong Yang

      Version of Record online: 27 NOV 2012 | DOI: 10.1111/cbdd.12084

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      In this study, the common features of three known ALK inhibitors that were crystallized with ALK have been identified for constructing a novel pharmacophore model. The established pharmacophore model Hypo1 had been carefully validated, and then compared with Hypo1′ that was built using a traditional ligand-based pharmacophore modeling method, which results further demonstrated the correctness of Hypo1. This pharmacophore model was adopted to screen in silico chemical databases for novel ALK inhibitors.

    3. Molecular Modeling of a Phenyl-Amidine Class of NMDA Receptor Antagonists and the Rational Design of New Triazolyl-Amidine Derivatives (pages 185–197)

      Paula A. Abreu, Helena C. Castro, Roberto Paes-de-Carvalho, Carlos R. Rodrigues, Viveca Giongo, Izabel C. N. P. Paixão, Marcos V. Santana, Jainne M. Ferreira, Octavia M. Caversan, Raquel A. C. Leão, Luana M. S. Marins, André M. Henriques, Florence M. C. Farias, Magaly G. Albuquerque and Sergio Pinheiro

      Version of Record online: 17 DEC 2012 | DOI: 10.1111/cbdd.12056

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      We performed a QSAR analysis of 17 phenyl-amidines described as NMDA receptor antagonists, and designed new triazolyl-amidines. Combination of synthetic chemistry, biological assays and molecular modeling studies is presented.

    4. Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1-(γ-1,2,3-Triazol Substituted Prolyl)-(S)-3,3-Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase-4 Inhibitors (pages 198–207)

      Lei Zhang, Mingbo Su, Jingya Li, Xun Ji, Jiang Wang, Zeng Li, Jia Li and Hong Liu

      Version of Record online: 19 NOV 2012 | DOI: 10.1111/cbdd.12058

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      Three compounds displayed not only good DPP-4 inhibitory activity but also excellent selectivity versus other proteases including DPP-8, DPP-9, and FAP.

    5. Comparison of the Molecular Dynamics and Calculated Binding Free Energies for Nine FDA-Approved HIV-1 PR Drugs Against Subtype B and C-SA HIV PR (pages 208–218)

      Shaimaa M. Ahmed, Hendrik G. Kruger, Thirumala Govender, Glenn E. M. Maguire, Yasien Sayed, Mahmoud A. A. Ibrahim, Previn Naicker and Mahmoud E. S. Soliman

      Version of Record online: 19 NOV 2012 | DOI: 10.1111/cbdd.12063

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      The first account of a comparative analysis of the binding affinities of nine FDA approved drugs against South African subtype C HIV PR as well as subtype B is presented. MD and binding free energy calculations provided more insight on the relative binding themes of the nine FDA inhibitors against both subtype B and subtype C. Difference of flap flexibility between the HIV PR subtype B and subtype C contributed most to the variation of binding affinities of the inhibitors.

    6. Synthesis and Antitubercular Activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium Chlorides (pages 219–227)

      Venugopala K. Narayanaswamy, Susanta K. Nayak, Melendhran Pillay, Renuka Prasanna, Yacoob M. Coovadia and Bharti Odhav

      Version of Record online: 14 NOV 2012 | DOI: 10.1111/cbdd.12065

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      Novel 3,6-dihydropyrimidine analogues were synthesized and characterized in salt form. The compounds were characterized by IR, NMR and elemental analysis. Compounds 7 and 11 exhibited anti-TB activity against MDR-TB at 16 μg/mL and have been subjected for single crystal X-ray studies.

    7. Effects of Flavone Derivatives on Antigen-Stimulated Degranulation in RBL-2H3 Cells (pages 228–237)

      Doseok Hwang, Hye-Jin Park, Eun-Kyung Seo, Joo Y. Oh, Sang Y. Ji, Dong K. Park and Yoongho Lim

      Version of Record online: 19 NOV 2012 | DOI: 10.1111/cbdd.12067

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      The activation level of mast cells is reflected in their degree of degranulation. This can in turn be determined by measuring the amount of β-hexosaminidase release, a key parameter in degranulation. In this study, 40 flavone derivatives were evaluated for their inhibition of degranulation in RBL-2H3 cells. 3′,7-Dihydroxyflavone inhibited degranulation (IC50 = 13.56 μM), which was comparable to PP2 used as a control. We report quantitative relationships between the structural properties of flavones and their inhibitory effects on degranulation.

    8. Structure-Based Design and Synthesis of Benzothiazole Phosphonate Analogues with Inhibitors of Human ABAD-Aβ for Treatment of Alzheimer’s Disease (pages 238–249)

      Koteswara R. Valasani, Gang Hu, Michael O. Chaney and Shirley S. Yan

      Version of Record online: 14 NOV 2012 | DOI: 10.1111/cbdd.12068

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      Structure-based screening has been used to identify the inhibitors of human ABAD-Aβ interaction, protects against aberrant mitochondrial and neuronal function and improves learning memory in the Alzheimer’s disease (AD) mouse model. The 2D QSAR and 3D pharmacophore models will assist in hi-throughput screening. Finally, ABAD molecular docking study of these novel molecules is undertaken to determine whether these compounds exhibit significant binding affinity with the binding site.

    9. Structure-Based Identification of Aporphines with Selective 5-HT2A Receptor-Binding Activity (pages 250–256)

      Vani Munusamy, Beow Keat Yap, Michael J. C. Buckle, Stephen W. Doughty and Lip Yong Chung

      Version of Record online: 14 NOV 2012 | DOI: 10.1111/cbdd.12069

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      A series of aporphines was investigated using a combination of in silico and in vitro screening approaches and (R)-roemerine and (±)-nuciferine were found to have selective 5-HT2A receptor binding affinity (Ki = 62 nM annd 139 nM, respectively).

    10. Synthesis and Evaluation of Thiouracil Derivatives as Dipeptidyl Peptidase IV Inhibitors (pages 257–264)

      Mani Sharma, Divya Singh and Monica Gupta

      Version of Record online: 14 NOV 2012 | DOI: 10.1111/cbdd.12070

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      A series of thiouracil derivatives were synthesized and evaluated for inhibition of dipeptidyl peptidase IV (DPP IV) for treatment of Type 2 diabetes.

    11. A New Approach to Counteract Bacteria Resistance: A Comparative Study Between Moxifloxacin and a New Moxifloxacin Derivative in Different Model Systems of Bacterial Membrane (pages 265–274)

      Silvia C. Lopes, Carla Ribeiro and Paula Gameiro

      Version of Record online: 27 NOV 2012 | DOI: 10.1111/cbdd.12071

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      Distinct factors govern the interaction of moxifloxacin and its metalloantibiotic with model systems of bacterial membranes, which clearly points out for a different translocation route. The metalloantibiotic is more sensitive to different model systems of bacterial membranes composition and shows no partition to model systems of mammalian cells. Cardiolipin’s absence from model systems of bacterial membranes bias conclusions that can be taken from lipid-drug interactions.

    12. Design, Synthesis and Biological Evaluation of Cinnamic Acyl Shikonin Derivatives (pages 275–283)

      Hong-Yan Lin, Wei Chen, Jing Shi, Wen-Yao Kong, Jin-Liang Qi, Xiao-Ming Wang and Yong-Hua Yang

      Version of Record online: 26 NOV 2012 | DOI: 10.1111/cbdd.12077

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      A series of cinnamic acyl shi-konin derivatives have been synthesized and their biological activities were also evaluated as potential anti-cancer agents. Among them, 8b showed the most potent anti- proliferate activity of SW872-s, A875 and A549 cell lines. Furthermore, the western blotting result showed 8b induced the apoptosis of A875 cell line by up-regulating the quantity of cleaved caspase-3, 7, 9 and cleaved PARP.

    13. Protein–Ligand Interaction Study of CpOGA in Complex with GlcNAcstatin (pages 284–290)

      Paulo Robson M. Sousa, Nelson Alberto N. de Alencar, Anderson H. Lima, Jerônimo Lameira and Cláudio Nahum Alves

      Version of Record online: 27 NOV 2012 | DOI: 10.1111/cbdd.12078

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      Hybrid QM/MM, molecular dynamics simulations and potential of mean force were employed to study the interactions established between GlcNAcstatin and a bacterial O-GlcNAcase enzyme. The result shows that a strong interaction. The results suggest that GlcNAcstatin (protonated) shows a tight interaction with Asp-298 (catalytic residue).

    14. Investigating Mammalian Tyrosine Phosphatase Inhibitors as Potential ‘Piggyback’ Leads to Target Trypanosoma brucei Transmission (pages 291–301)

      Irene Ruberto, Balazs Szoor, Rachel Clark and Keith R. Matthews

      Version of Record online: 10 JAN 2013 | DOI: 10.1111/cbdd.12079

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      Trypanosomes are parasites of sub-Saharan Africa responsible for important human and animal disease. TbPTP1 is a tyrosine phosphatase that acts as a master regulator of trypanosome life cycle development that when inhibited causes a premature developmental response that is lethal to the parasite. We demonstrate that inhibitors targeting mammalian PTP1B can also inhibit TbPTP1, providing a potential piggyback strategy to exploit drugs for obesity and diabetes for the treatment for neglected tropical disease.

  3. Research Letter

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letter
    1. New Alloferon Analogues: Synthesis and Antiviral Properties (pages 302–309)

      Mariola Kuczer, Anna Majewska and Renata Zahorska

      Version of Record online: 19 NOV 2012 | DOI: 10.1111/cbdd.12020

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      A series of new alloferon derivatives were synthesized. Synthesized compounds were tested in vitro for antiviral and cytotoxic activity. Some of these analogues could be worthy candidates for developing new drugs as antiviral agents.