Chemical Biology & Drug Design

Cover image for Vol. 90 Issue 4

October 2017

Volume 90, Issue 4

Pages 485–636

  1. ISSUE INFORMATION

    1. Top of page
    2. ISSUE INFORMATION
    3. EDITOR'S CHOICE
    4. RESEARCH ARTICLES
    5. RESEARCH LETTER
    1. Issue Information (pages 485–488)

      Version of Record online: 10 SEP 2017 | DOI: 10.1111/cbdd.12858

  2. EDITOR'S CHOICE

    1. Top of page
    2. ISSUE INFORMATION
    3. EDITOR'S CHOICE
    4. RESEARCH ARTICLES
    5. RESEARCH LETTER
    1. Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates (pages 489–495)

      Travis Korosh, Emmanuel Bujans, Mary Morada, Canan Karaalioglu, Jean Jacques Vanden Eynde, Annie Mayence, Tien L. Huang and Nigel Yarlett

      Version of Record online: 25 APR 2017 | DOI: 10.1111/cbdd.12972

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      A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10H20) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates. Compound 3m, 2,2′-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, had good in vitro (9 μm) and in vivo (25 mg/kg per day for 4 days) activity. Compound 3m was reduced by pyruvate:ferredoxin oxidoreductase by a ferredoxin independent mechanism.

  3. RESEARCH ARTICLES

    1. Top of page
    2. ISSUE INFORMATION
    3. EDITOR'S CHOICE
    4. RESEARCH ARTICLES
    5. RESEARCH LETTER
    1. Design, synthesis, and in vitro antituberculosis activity of benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4-oxadiazole derivatives (pages 496–500)

      Yasodakrishna Sajja, Sowmya Vanguru, Hanmanth Reddy Vulupala, Lingaiah Nagarapu, Yogeswari Perumal, Dharmarajan Sriram and Jagadeesh Babu Nanubolu

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12969

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      Benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4-oxadiazole hybrids (4a–o) were synthesized using di(acetoxy)iodobenzene-mediated oxidative cyclization. All the synthesized compounds 4(a–o) were screened for their in vitro antitubercular activity against M. tuberculosis H37Rv (ATCC 27294) by using agar dilution method. Compounds 4o, 4l, and 4m were found to be more active than standard drug ethambutol and have shown lower cytotoxicity.

    2. MD simulations and multivariate studies for modeling the antileishmanial activity of peptides (pages 501–510)

      Mirian Elisa Rodrigues Guerra, Valmir Fadel, Vinícius Gonçalves Maltarollo, Gisele Baldissera, Kathia Maria Honorio, José Roberto Ruggiero and Marcia Perez dos Santos Cabrera

      Version of Record online: 8 APR 2017 | DOI: 10.1111/cbdd.12970

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      A quantitative structure–activity relationship model was constructed for predicting the antileishmanial activity of peptides through an innovative theoretical approach. Molecular descriptors were prospected from physicochemical properties and from parameters of the folded peptide chains, calculated after molecular dynamics simulations in a membrane-mimetic environment. They were used as input for the model generation, which predicts that cationic charge, backbone solvation, solvent-accessible surface area, and volume are important for activity.

    3. Modified benzoxazolone derivative as 18-kDa TSPO ligand (pages 511–519)

      Neelam Kumari, Nidhi Chadha, Pooja Srivastava, Lokesh Chandra Mishra, Sunita Bhagat, Anil K. Mishra and Anjani K. Tiwari

      Version of Record online: 19 APR 2017 | DOI: 10.1111/cbdd.12971

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      A new congener of acetamidobenzoxazolone called as NBMP or 2-[5 (naphthyl)amino-2-oxobenzo-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-penylacetamide has shown 10.8 ± 1.2 nm binding affinity towards TSPO under in vitro conditions.

    4. One-pot cascade synthesis and in vitro evaluation of anti-inflammatory and antidiabetic activities of S-methylphenyl substituted acridine-1,8-diones (pages 520–526)

      Lavanya Mallu, Dhakshanamurthy Thirumalai and Indira Viswambaran Asharani

      Version of Record online: 12 APR 2017 | DOI: 10.1111/cbdd.12973

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      One-pot cascade reaction of 4-(methylthio)benzaldehyde and dimedone with various amines afforded S-methylphenyl substituted acridine-1,8-diones in ethanol.

    5. N-hydroxy-substituted 2-aryl acetamide analogs: A novel class of HIV-1 integrase inhibitors (pages 527–534)

      Utsab Debnath, Prachi Kumar, Aakanksha Agarwal, Ajay Kesharwani, Satish K. Gupta and Seturam B. Katti

      Version of Record online: 26 APR 2017 | DOI: 10.1111/cbdd.12974

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      Based on an in silico approach, novel classes of N-hydroxy-substituted 2-aryl acetamide analogues were identified as anti-HIV-1 integrase inhibitors. To do that, de novo-designed molecules were chemically and biologically evaluated to find out a hit (compound 4b). The structure of compound 4b was further optimized for better binding affinity toward the integrase binding pocket. Finally, biological evaluation followed by docking studies revealed compounds 6–2c and 6–5b as new leads of HIV-1 integrase inhibitors.

    6. Quantitative structure–activity relationship and molecular docking studies on designing inhibitors of the perforin (pages 535–544)

      Fucheng Song, Lianhua Cui, Jinmei Piao, Hui Liang, Hongzong Si, Yunbo Duan and Honglin Zhai

      Version of Record online: 12 APR 2017 | DOI: 10.1111/cbdd.12975

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      The molecular docking analysis of compound 42a shows a detailed binding mode with three hydrogen bond interactions (red dashes) formed with residues TRP-112 and ASP-132.

    7. Deleterious effects of non-synonymous single nucleotide variants of human IL-1β gene (pages 545–553)

      Yue-Hui Zhang, Jia Song, Jing Zhang and Jiang Shao

      Version of Record online: 22 MAY 2017 | DOI: 10.1111/cbdd.12976

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      The IL-1β is currently a hot molecule in IDD research, and the effects of its nsSNVs are studied here. Based on the constructed 3D structure of pro-IL-1β, F162S was proposed to reduce stability of pro-IL-1β protein with multiple analyses. While based on the experimental 3D structure of mature IL-1β and its neutralizing McAb canakinumab complex, L31F was found to attenuate the interaction of IL-1β with canakinumab by reducing binding energy, while F162S could not.

    8. Live cell imaging of bacterial cells: Pyrenoylpyrrole-based fluorescence labeling (pages 554–560)

      Mathiyazhagan Arun Divakar and Sivakumar Shanmugam

      Version of Record online: 7 MAY 2017 | DOI: 10.1111/cbdd.12978

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      Novel pyrenoylpyrrole compounds were synthesized from easily available synthons. All the compounds were non-cytotoxic, potential candidates for microbial cell imaging to aid diagnostics with moderate antibacterial activity.

    9. The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel (pages 561–571)

      Patrícia S. Guerreiro, Eduardo Corvacho, João G. Costa, Nuno Saraiva, Ana S. Fernandes, Matilde Castro, Joana P. Miranda and Nuno G. Oliveira

      Version of Record online: 3 MAY 2017 | DOI: 10.1111/cbdd.12979

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      The human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional DNA repair enzyme with relevant redox signalling functions. The quinone derivative E3330, a redox inhibitor of APE1, decreased the colony formation and chemoinvasion of docetaxel-treated MDA-MB-231 cells (represented in blue). In addition, E3330 as single agent (represented in red) significantly reduced the collective cell migration. These results suggest APE1 redox function as a potential target for the modulation of cell migration and invasion in metastatic breast cancer.

    10. Synthesis, in vitro evaluation, and 68Ga-radiolabeling of CDP1 toward PET/CT imaging of bacterial infection (pages 572–579)

      Jyotibon Dutta, Sooraj Baijnath, Anou M. Somboro, Savania Nagiah, Fernando Albericio, Beatriz G. de la Torre, Biljana Marjanovic-Painter, Jan Rijn Zeevaart, Mike Sathekge, Hendrik G. Kruger, Anil Chuturgoon, Tricia Naicker, Thomas Ebenhan and Thavendran Govender

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12980

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      A bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) was utilized to functionalize the antimicrobial peptide, which in turn was capable of chelating gallium. The synthesized natGa-CDP1 showed bacterial selectivity and low affinity toward hepatic cells, which are favorable characteristics for further preclinical application.

    11. Design, synthesis, biological evaluation, and molecular docking of novel flavones as H3R inhibitors (pages 580–589)

      Gang Wen, Qian Liu, Huabin Hu, Dongmei Wang and Song Wu

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12981

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      A series of novel flavone derivatives were designed, synthesized, and evaluated for their H3R inhibitory activity. To elucidate the interactions between compounds and H3R, we built a homology model of H3R and performed molecular docking studies.

    12. Piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates: Synthesis and antiplasmodial evaluation (pages 590–595)

      Amandeep Singh, Anu Rani, Jiri Gut, Philip J. Rosenthal and Vipan Kumar

      Version of Record online: 26 APR 2017 | DOI: 10.1111/cbdd.12982

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      Synthesis of piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates and their evaluation against chloroquine-resistant and mefloquine-sensitive W2 strain of Plasmodium falciparum.

    13. Identification of natural inhibitors of Bcr-Abl for the treatment of chronic myeloid leukemia (pages 596–608)

      Phanikrishna Parcha, Sailu Sarvagalla, Bindu Madhuri, Sankar Pajaniradje, Vinitha Baskaran, Mohane Selvaraj Coumar and Baskaran Rajasekaran

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.12983

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      In this study, we performed virtual screening of ZINC natural compounds by docking to the Abl kinase ATP-binding site using Glide software. Two natural inhibitors ZINC08764498 (hit1) and ZINC12891610 (hit2) were selected by considering their high Glide docking score and stable interaction with the hinge region residue Met-318 of Abl kinase catalytic domain. The compounds were further validated using density functional theory and 10-ns molecular dynamic simulations. In vitro testing results showed that compound ZINC08764498 (hit1) has selective pro-apoptotic activity on Bcr-Abl-overexpressing K-562 cells and no significant cytotoxicity on Bcr-Abl-negative HEK-293 cell line.

    14. Rational drug design of indazole-based diarylurea derivatives as anticancer agents (pages 609–617)

      Yan-yan Chu, He-juan Cheng, Zhen-hua Tian, Jian-chun Zhao, Gang Li, Yang-yang Chu, Chang-jun Sun and Wen-bao Li

      Version of Record online: 2 MAY 2017 | DOI: 10.1111/cbdd.12984

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      Based on the structure-based drug design, we designed and prepared a series of novel indazole-based diarylurea derivatives targeting c-kit, and their antiproliferative activities were evaluated. We used molecular docking method to explore the interaction mechanisms and SAR. Compound 1i possessed improved solubilities and best activities. It is a promising anticancer agent and under further development.

    15. A comparison inhibitory effects of cisplatin and MNPs-PEG-cisplatin on the adhesion capacity of bone metastatic breast cancer (pages 618–628)

      Mohammad Javad Mokhtari, Fatemeh Koohpeima and Hadi Mohammadi

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.12985

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      A new formulation of cisplatin loaded onto Fe3O4MNPs-PEG has been synthesized and characterized. The in vitro evaluation of the study found that cisplatin and cisplatin-loaded MNPs-PEG decreased the rate of metastasis, migration, and adhesion of T47D to distant organs. MNPs-PEG-cisplatin strongly increased anti-cancer effects compared with free cisplatin in the T47D cell line.

  4. RESEARCH LETTER

    1. Top of page
    2. ISSUE INFORMATION
    3. EDITOR'S CHOICE
    4. RESEARCH ARTICLES
    5. RESEARCH LETTER
    1. Epidermal growth factor receptor (EGFR) structure-based bioactive pharmacophore models for identifying next-generation inhibitors against clinically relevant EGFR mutations (pages 629–636)

      Pooja S. Panicker, Anu R. Melge, Lalitha Biswas, Pavithran Keechilat and Chethampadi G. Mohan

      Version of Record online: 3 MAY 2017 | DOI: 10.1111/cbdd.12977

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      EGFR and its mutants showed resistance to FDA approved drugs. Development of EGFR and its mutant structure based e-pharmacophore model for virtual screening of drug like molecules. CUDC101 and ML167 can be a potent EGFR inhibitor overcoming its mutant resistance. Developed 3D e-pharmacophore models can be used for identifying new scaffold-based molecules.

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