Chemical Biology & Drug Design

Cover image for Chemical Biology & Drug Design

September 2011

Volume 78, Issue 3

Pages i–iii, 323–493

  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: 11 AUG 2011 | DOI: 10.1111/j.1747-0285.2011.01190.x

  2. Research Articles

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. You have full text access to this OnlineOpen article
      Non-Bisphosphonate Inhibitors of Isoprenoid Biosynthesis Identified via Computer-Aided Drug Design (pages 323–332)

      Jacob D. Durrant, Rong Cao, Alemayehu A. Gorfe, Wei Zhu, Jikun Li, Anna Sankovsky, Eric Oldfield and J. Andrew McCammon

      Version of Record online: 3 AUG 2011 | DOI: 10.1111/j.1747-0285.2011.01164.x

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      Computational techniques are used to identify a non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, several of these predicted inhibitors are also potent inhibitors of undecaprenyl diphosphate synthase.

    2. You have free access to this content
      Molecular Modeling Studies on Benzimidazole Carboxamide Derivatives as PARP-1 Inhibitors Using 3D-QSAR and Docking (pages 333–352)

      Huahui Zeng, Huabei Zhang, Fubin Jang, Lingzhou Zhao and Jianyuan Zhang

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01139.x

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      Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP-1 (one of the PARPs) inhibitors have been carried out combined molecular docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling study. The information will help us to predict the activity of new inhibitors and further design some novel and potent PARP-1 enzyme inhibitors.

    3. Designing and Engineering of a Site-specific Incorporation of a Keto Group in Uricase (pages 353–360)

      Zhengzhi Fang, Yaguang Liu, Jingxian Liu, Renhua Sun, Hai Chen, Xiangdong Gao and Wenbing Yao

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01141.x

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      A new pAcPhe specific M. jannaschii tyrosyl-tRNA synthetase was designed and generated to incorporate pAcPhe into two sites of the Candida utilis uricase, Lys21 and Lys248 based on a homology modeling and docking model. The mutated uricase exhibited decreased antigenic properties while its catalytic activities remained unchanged. This method may benefit a rational PEGIyation to improve the pharmacological properties of urate oxidase.

    4. Role of Interactions and Volume Variation in Discriminating Active and Inactive Forms of Cyclin-Dependent Kinase-2 Inhibitor Complexes (pages 361–369)

      Nallusamy Saranya and Samuel Selvaraj

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01145.x

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      In CDK-2 ligand complexes, binding affinity had high correlation with interactions and volume changes [protein binding cavity volume (PCV) and ligand volume (LV)] in active and inactive conformation respectively. Consideration of inactive conformation in docking and scoring studies may result in screening of highly selective and potent inhibitors.

    5. Study of Human Dopamine Sulfotransferases Based on Gene Expression Programming (pages 370–377)

      Hongzong Si, Jiangang Zhao, Lianhua Cui, Ning Lian, Hanlin Feng, Yun-Bo Duan and Zhide Hu

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01155.x

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      A quantitative model is developed to predict the Km of 47 human dopamine sulfotransferases by gene expression programming. The best quantitative model with squared standard error and square of correlation coefficient are 0.096 and 0.91 for training data set, 0.102 and 0.88 for test set respectively.

    6. Structure-Based Virtual Screening of Glycogen Synthase Kinase 3β Inhibitors: Analysis of Scoring Functions Applied to Large True Actives and Decoy Sets (pages 378–390)

      Dmitry I. Osolodkin, Vladimir A. Palyulin and Nikolay S. Zefirov

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01159.x

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      A thorough comparative analysis of different scoring functions applied to diverse set of glycogen synthase kinase 3β inhibitors reveals their abilities to discriminate true active molecules from decoys. Analysis of overall enricment, early enrichment and true actives versus true inactives enrichment is performed.

    7. Discovery of New Antifungal Leads via Pharmacophore Modeling and QSAR Analysis of Fungal N-Myristoyl Transferase Inhibitors Followed by In Silico Screening (pages 391–407)

      Mutasem O. Taha, Amjad M. Qandil, Tariq Al-Haraznah, Reema Abu Khalaf, Hiba Zalloum and Amal G. Al-Bakri

      Version of Record online: 13 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01160.x

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      New potent anti fungal leads we unveiled via pharmacophore modeling and QSAR analysis of fungal N-Myristoyl Transferase inhibitors followed by in silico screening.

    8. Pharmacophore Modeling and Density Functional Theory Analysis for A Series of Nitroimidazole Compounds with Antitubercular Activity (pages 408–417)

      Nilesh R. Tawari and Mariam S. Degani

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01161.x

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      Pharmacophore modeling, 3D-QSAR and DFT studies are reported for PA-824 and its analogs. Results of this study are expected to be useful in the design of novel potent nitroimidazoles as antitubercular agents.

    9. 3D-QSAR and Docking Studies on the HEPT Derivatives of HIV-1 Reverse Transcriptase (pages 418–426)

      Ramaswamy Sree Latha, Ramadoss Vijayaraj, Ettayapuram Ramaprasad Azhagiya Singam, Krishnaswamy Chitra and Venkatesan Subramanian

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01162.x

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      The bulky group substitutions at 3′ and 5′ of R4 combined with the branched chain bulky group substitutions at R2 position enhances the activity of HEPT inhibitors.

    10. Revealing the Drug-Resistant Mechanism for Diarylpyrimidine Analogue Inhibitors of HIV-1 Reverse Transcriptase (pages 427–437)

      Hao Zhang, Fang Qin, Wei Ye, Zeng Li, Songyao Ma, Yan Xia, Yi Jiang, Jiayi Zhu, Yixue Li, Jian Zhang and Hai-Feng Chen

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01163.x

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      The drug-resistant mechanism of DAPY analogue inhibitors was investigated. Compound 22 and 15A can form a direct or indirect (through water) hydrogen bond with Asn103. Both 22 and 15A have not drug resistance with K103N mutant.

    11. Safety and Efficacy of New 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine Analogs as Potential Phosphodiesterase-4 Inhibitors in NIH-3T3 Mouse Fibroblastic Cells (pages 438–444)

      Maryam Baeeri, Alireza Foroumadi, Maryam Motamedi, Azadeh Yahya-Meymandi, Loghman Firoozpour, Seyed N. Ostad, Abbas Shafiee, Saeid Souzangarzadeh and Mohammad Abdollahi

      Version of Record online: 29 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01167.x

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      A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, were developed and tested in NIH-3T3 mouse fibroblastic for efficacy and safety in comparison to rolipram. The cytotoxic IC50 of all synthesized compounds were approximately two folds greater than their required concentration for inhibition of PDE-4 (in term of elevation of cAMP) and thus these structures could be used to develop potent and safe inhibitors of PDE-4 enzyme. These compounds should be further investigated for their selectivity for different intact cAMP-PDE isoforms.

    12. Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat (pages 445–453)

      Ram Raghubir, Rajkumar Verma, Sheeba S. Samuel, Saman Raza, Wajahul Haq and Seturam B. Katti

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01153.x

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      The newly developed thiazolidine-4-one derivatives were synthesized and screened for their anti-stroke activity. These derivatives may provide a new pharmacophore for the development of a new class of potent anti-stroke agents.

  3. Research Letters

    1. Top of page
    2. Issue Information
    3. Research Articles
    4. Research Letters
    1. High-Throughput Analysis of an RNAi Library Identifies Novel Kinase Targets in Trypanosoma brucei (pages 454–463)

      Zachary B. Mackey, Kyriacos Koupparis, Mari Nishino and James H. McKerrow

      Version of Record online: 14 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01156.x

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      Two previously undescribed kinases in Trypanosoma brucei (TbERK8 and TbCRK12) were identified as essential for normal proliferation in the parasite. These kinases were identified by utilizing a luciferase-based assay to screen a small RNAi library consisting of 31 T. brucei kinases.

    2. Design, Synthesis, and Evaluation of Thiazolidinone Derivatives as Antimicrobial and Anti-viral Agents (pages 464–470)

      Veerasamy Ravichandran, Abhishek Jain, Krishnan S. Kumar, Harish Rajak and Ram K. Agrawal

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01149.x

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      Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro antimicrobial activity of this class of potent antimicrobial agents.

    3. Knowledge-Based Identification of the ERK2/STAT3 Signal Pathway as a Therapeutic Target for Type 2 Diabetes and Drug Discovery (pages 471–476)

      Takayoshi Kinoshita, Kentaro Doi, Hajime Sugiyama, Shuhei Kinoshita, Mutsuyo Wada, Shuji Naruto and Atsushi Tomonaga

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01151.x

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      The text mining with a unique query identified the ERK2/STAT3 pathway as a novel diabetes target. The mechanism-based peptide inhibitor of ERK2 conferred a significant effect on the db/db model mouse.

    4. Synthesis and Evaluation of Antimalarial Activity of Oxygenated 3-alkylpyridine Marine Alkaloid Analogues (pages 477–482)

      Flaviane F. Hilário, Renata Cristina de Paula, Mariana L. T. Silveira, Gustavo H. R. Viana, Rosemeire B. Alves, Juliana R. C. S. Pereira, Luciana Maria Silva, Rossimiriam P. de Freitas and Fernando de Pilla Varotti

      Version of Record online: 8 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01154.x

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      A series of new oxygenated analogues of marine 3-alkylpyridine alkaloids were prepared from 3-pyridinepropanol in few steps and in good yields. All new compounds were evaluated for their antiplasmodial activity and cytotoxicity. A significant reduction in parasitemia was observed for some of the prepared compounds and the majority of them exibited a selectivity index (SI) ranging from 2.78 to 15.58, which suggests that these compounds may be a promising class of substances with antimalarial activity.

    5. CoMFA, CoMSIA, and Docking Studies on Thiolactone-Class of Potent Anti-malarials: Identification of Essential Structural Features Modulating Anti-malarial Activity (pages 483–493)

      Kuldeep K. Roy, Shome S. Bhunia and Anil K. Saxena

      Version of Record online: 13 JUL 2011 | DOI: 10.1111/j.1747-0285.2011.01158.x

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      The integrated ligand- and structure-based drug design approaches are applied on thiolactone-class of antimalarials, to explore the structural features essential for the inhibition of P. falciparum. The furnished results present good scope for rational design of thiolactone-class of compounds that could furnish better anti-malarial activity.

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