Chemical Biology & Drug Design

Cover image for Vol. 86 Issue 6

Early View (Online Version of Record published before inclusion in an issue)

Edited By: David Selwood

Impact Factor: 2.485

ISI Journal Citation Reports © Ranking: 2014: 28/59 (Chemistry Medicinal); 164/290 (Biochemistry & Molecular Biology)

Online ISSN: 1747-0285


  1. 1 - 42
  1. Research Articles

    1. Iminothiazoline-Sulfonamide Hybrids as Jack Bean Urease Inhibitors; Synthesis, Kinetic Mechanism and Computational Molecular Modeling

      Aamer Saeed, Shams-ul Mahmood, Muhammad Rafiq, Zaman Ashraf, Farukh Jabeen and Sung-Yum Seo

      Article first published online: 26 NOV 2015 | DOI: 10.1111/cbdd.12675

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      2-iminothiazoline-sulfonamide hybrids (3aj) were synthesized by the heterocyclization of sulfanilamide thioureas with propragyl bromide. The compounds (3h) and (3i) exhibited excellent activity with IC50 0.064 and 0.058 µm respectively while IC50 of thiourea is 20.9 µm. Docking score (−10.6466 to −8.7215 Kcal/mol) and binding energy (London dG ranging from −14.4825 to −10.4087 Kcal/mol) are good.

  2. Research Letters

    1. Sirtuins are Unaffected by PARP Inhibitors Containing Planar Nicotinamide Bioisosteres

      Torun Ekblad and Herwig Schüler

      Article first published online: 26 NOV 2015 | DOI: 10.1111/cbdd.12680

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      We show that the activities of the four human sirtuin isoforms SIRT1, SIRT2, SIRT3 and SIRT6 are unaffected by the clinical PARP inhibitors, niraparib, olaparib, rucaparib, talazoparib, and veliparib, and the widely used research tools, PJ34 and XAV939.

  3. Research Articles

    1. Synthesis, Biological Evaluation, and Molecular Docking of (R)-2-((8-(3-aminopiperidin-1-yl)-3-methyl-7-(3-methylbut-2-en-1-yl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)methyl)benzonitrile as Dipeptidyl Peptidase IV Inhibitors

      Yan Ran, Heying Pei, Mingfeng Shao and Lijuan Chen

      Article first published online: 23 NOV 2015 | DOI: 10.1111/cbdd.12663

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      In this paper, we described the synthesis, biological evaluation and molecular docking of corresponding enantiomers of compounds 40 and 43. The most potent inhibitor is (R)-40 (IC50 = 23.5 nM, F = 74.67%, T1/2 = 4 h), which exhibited moderate antihyperglycemic activity as compared to the standard antidiabetic drug Linagliptin in OGTT. In addition, compound (R)-40 effectively improved the pathological state of DIO mice. Molecular docking studies clarified the favorable binding affinity between compound (R)-40 and DPP-IV active site.

    2. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties

      Georgi Stavrakov, Violeta Valcheva, Yulian Voynikov, Irena Philipova, Mariyana Atanasova, Spiro Konstantinov, Plamen Peikov and Irini Doytchinova

      Article first published online: 23 NOV 2015 | DOI: 10.1111/cbdd.12676

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      A model for antitubercular activity prediction was developed and applied to a combinatorial library of 40 theophylline-7-acetic acid derivatives. The best predicted compounds were synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them showed antimycobacterial activity in the nanomolar range and were 60 times more active than ethambutol.

    3. Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with Diimine Coligands: DNA Binding, Cytotoxic Cell Apoptosis, and Apoptotic Mechanism

      Hao Yu, Yong Yang, Qiaoyu Li, Tieliang Ma, Jun Xu, Taofeng Zhu, Jing Xie, Wenjiao Zhu, Zhihong Cao, Kun Dong, Jiancui Huang and Lei Jia

      Article first published online: 20 NOV 2015 | DOI: 10.1111/cbdd.12669

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      A serial of mixed ligand Cu(II) complexes have been isolated and characterized. The interaction of the complexes with calf thymus DNA has been explored by using physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction.

    4. Effects of N-Methylated Amyloid-β30–40 Peptides on the Fibrillation of Amyloid-β1–40

      Hirotsugu Hiramatsu, Hironori Ochiai and Tomoyuki Komuro

      Article first published online: 20 NOV 2015 | DOI: 10.1111/cbdd.12674

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      Inhibitory effect of N-Me Aβ30–40 peptides on Aβ1–40 fibrillation was dependent on the concentration of N-Me peptide and the number and position of N-Me groups. Monomer–dimer equilibrium of N-Me peptides was (partly) responsible for the observed dependence. Monomeric N-Me peptides decreased ThT fluorescence count during Aβ1–40 fibrillation by co-aggregating and disrupting the regular β-sheet structure of Aβ1–40 fibrils.

  4. Research Letters

    1. Synthesis of Naphthyl-, Quinolin- and Anthracenyl Analogues of Clofibric Acid as PPARα Agonists

      Letizia Giampietro, Alessandra Ammazzalorso, Isabella Bruno, Simone Carradori, Barbara De Filippis, Marialuigia Fantacuzzi, Antonella Giancristofaro, Cristina Maccallini and Rosa Amoroso

      Article first published online: 20 NOV 2015 | DOI: 10.1111/cbdd.12677

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      New analogues of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized and evaluated for PPARα transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPARα.

  5. Research Articles

    1. Novel Peptides from Skins of Amphibians Showed Broad-Spectrum Antimicrobial Activities

      Ying Wang, Yue Zhang, Wen-Hui Lee, Xinwang Yang and Yun Zhang

      Article first published online: 13 NOV 2015 | DOI: 10.1111/cbdd.12672

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      12 novel peptides with broad-spectrum antimicrobial activities were identified from the skin of three frogs. A novel antimicrobial peptide family, named as Limnochariin, were characterized for the first time. Amphibian skin peptides provide novel templates for developing new drugs that can overcome the rising resistance of pathogenic microorganisms to classic antibiotic treatments.

    2. Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors

      Syahrul Imran, Muhammad Taha, Nor Hadiani Ismail, Syed Muhammad Kashif, Fazal Rahim, Waqas Jamil, Habibah Wahab and Khalid Mohammed Khan

      Article first published online: 13 NOV 2015 | DOI: 10.1111/cbdd.12666

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      Synthesis and α-glucosidase inhibition activity of new flavone ether derivatives (315).

    3. Geniposide Attenuates the Phosphorylation of Tau Protein in Cellular and Insulin-deficient APP/PS1 Transgenic Mouse Model of Alzheimer's Disease

      Yonglan Zhang, Fei Yin, Jianhui Liu and Zixuan Liu

      Article first published online: 12 NOV 2015 | DOI: 10.1111/cbdd.12673

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      Geniposide attenuates the phosphorylation of tau protein by potentiating the insulin signaling in cellular and APP/PS1 transgenic mouse model of Alzheimer's disease.

    4. Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues

      Rémi Safi, Fréderic Rodriguez, Georges Hilal, Mona Diab-Assaf, Youssef Diab, Marwan El-Sabban, Fadia Najjar and Evelyne Delfourne

      Article first published online: 5 NOV 2015 | DOI: 10.1111/cbdd.12670

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      A series of novel ferutinin derivatives were synthesized, biologically evaluated and tested for their in silico targets, the estrogen receptors α and β. Two compounds exhibited improved cytotoxic activities on the proliferation of estrogen-dependent and -independent breast cancer cell lines, as compared to the parent compound. Molecular docking studies and functional assay on ferutinin and its potent analogue showed that the cytotoxic effect in estrogen-dependent cells may be correlated to the antagonist potential of the new compound towards ERα protein.

    5. Bioinformatics Prediction and In Vitro Analysis Revealed That miR-17 Targets Cyclin D1 mRNA in Triple Negative Breast Cancer Cells

      Fariba Karami, Samira Mohammadi-Yeganeh, Nairi Abedi, Ameneh Koochaki, Vahid Kia and Mahdi Paryan

      Article first published online: 2 NOV 2015 | DOI: 10.1111/cbdd.12671

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      miR-17 targets cyclin D1 which is involved in metastatic breast cancer. So, miR-17 is an attractive molecule that after intensive research can probably be used as a biomarker in triple negative breast cancer.

  6. Research Letters

    1. Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells

      Effat Alizadeh, MohamadReza Baghaban Eslaminejad, Abolfazl Akbarzadeh, Zohre Sadeghi, Mozghan Abasi, Roya Herizchi and Nosratollah Zarghami

      Article first published online: 19 OCT 2015 | DOI: 10.1111/cbdd.12664

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      Administration of TSA during hepatic differentiation of adipose tissue derived mesenchymal stem cells (AT-MSCs) resulted in the facilitation of hepatic differentiation, higher miR- 122 expression levels, and subsequently attenuation of AFP expression in hepatocyte like cells.

  7. Research Articles

    1. Design, Synthesis, and Biological Evaluation of Novel Cholesteryl Peptides with Anticancer and Multidrug Resistance-Reversing Activities

      Xin Deng, Qianqian Qiu, Xuekun Wang, Wenlong Huang and Hai Qian

      Article first published online: 19 OCT 2015 | DOI: 10.1111/cbdd.12667

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      We designed and synthesized a series of cholesteryl peptides, biological evaluation revealed that these peptides showed improved anti-cancer activity and retained the selectivity to cancer cell lines. In addition, the peptides also presented multidrug resistance-reversing effect on multidrug-resistant cells.

    2. Practical Synthesis, Antidepressant, and Anticonvulsant Activity of 3-Phenyliminoindolin-2-one Derivatives

      Jian-Yin Ma, Ying-Chun Quan, Hong-Guo Jin, Xing-Hua Zhen, Xue-Wu Zhang and Li-Ping Guan

      Article first published online: 19 OCT 2015 | DOI: 10.1111/cbdd.12668

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      A series of 3-phenyliminoindolin-2-one derivatives were synthesized and evaluated for their antidepressant and anticonvulsant activity. Compound 3r was found be to the most antidepressant-like activity. The probable mechanism of action of compound 3r is thought to be related to the increase in 5-HT and NE in the CNS. Fifteen compounds possessed anticonvulsant activity against PTZ-induced seizure.

    3. Novel Inhibitors of Ornithine Decarboxylase of Leishmania Parasite (LdODC): The Parasite Resists LdODC Inhibition by Overexpression of Spermidine Synthase

      Mousumi Das, Shalini Singh and Vikash Kumar Dubey

      Article first published online: 13 OCT 2015 | DOI: 10.1111/cbdd.12665

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      Novel inhibitors of ornithine decarboxylase of Leishmania donovani are identified. Effect of inhibitors on the parasite survival was studied. Leishmania resists these LdODC inhibitors by over-expression of spermidine synthase.

    4. Novel Scaffold Identification of mGlu1 Receptor Negative Allosteric Modulators Using a Hierarchical Virtual Screening Approach

      Jae Wan Jang, Nam-Chul Cho, Sun-Joon Min, Yong Seo Cho, Ki Duk Park, Seon Hee Seo, Kyoung Tai No and Ae Nim Pae

      Article first published online: 9 OCT 2015 | DOI: 10.1111/cbdd.12654

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      Novel scaffolds for mGluR1 modulators were successfully identified using virtual screening approach with pharmacophore modeling and Bayesian classification model combined with structure-based virtual screening.

    5. Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity

      Michael F. Mesleh, Premraj Rajaratnam, Mary Conrad, Vasu Chandrasekaran, Christopher M. Liu, Bhaumik A. Pandya, You Seok Hwang, Peter T. Rye, Craig Muldoon, Bernd Becker, Johannes Zuegg, Wim Meutermans and Terence I. Moy

      Article first published online: 9 OCT 2015 | DOI: 10.1111/cbdd.12662

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      Cell wall biogenesis for many clinically-relevant bacterial pathogens requires the activity of peptidoglycan glycosyltransferases. We report the synthesis of disaccharide-like compounds based on the peptidoglycan glycosyltransferase inhibitor moenomycin. We show, using a newly developed functional assay and NMR binding studies, that a subset of these compounds bind and inhibit peptidoglycan glycosyltransferase enzymes as expected.

    6. Chromanyl–isoxazolidines as Antibacterial agents: Synthesis, Biological Evaluation, Quantitative Structure Activity Relationship, and Molecular Docking Studies

      Gagandeep Singh, Anuradha Sharma, Harpreet Kaur and Mohan Paul S. Ishar

      Article first published online: 7 OCT 2015 | DOI: 10.1111/cbdd.12653

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      Regio- and stereoselective 1,3-dipolar cycloadditions of C-(chrom-4-one-3-yl)-N-phenylnitrones (N) with different mono-substituted, disubstituted and cyclic dipolarophiles leads to synthesis of substituted N-phenyl-3′-(chrom-4-one-3-yl)-isoxazolidines (1-40); were assayed for their in-vitro antibacterial activity and display significant inhibitory potential.

  8. Research Letters

    1. Design and Development of Mycobacterium tuberculosis Lysine ɛ-Aminotransferase Inhibitors for Latent Tuberculosis Infection

      Brindha Devi Parthiban, Shalini Saxena, Manoj Chandran, Padma Sridevi Jonnalagadda, Renu Yadav, Rudraraju Reshma Srilakshmi, Yogeeswari Perumal and Sriram Dharmarajan

      Article first published online: 7 OCT 2015 | DOI: 10.1111/cbdd.12655

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      Compound 21 found to be most active with MTB LAT IC50 of 0.81 ± 0.03 μm and also showed 2.3 log reduction in nutrient-starved MTB model.

  9. Research Articles

    1. Investigation of In vitro PDT Activities and In vivo Biopotential of Zinc Phthalocyanines Using 131I Radioisotope

      Mine Ince, Ozge Er, Kasim Ocakoglu, Fatma Yurt Lambrecht, Suleyman Gokhan Colak, Hale Melis Soylu, Cagla Kayabasi and Cumhur Gunduz

      Article first published online: 5 OCT 2015 | DOI: 10.1111/cbdd.12659

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      Radiolabeled Zn(II)Pc2 demonstrates a potential for nuclear imaging of ovary and pancreatic tumor. Zn(II)Pc1 and 2 are encouraging for novel approaches in PDT; it merits further explanation. Consequently, Zn(II)Pc2 might be using bifunctional agents for nuclear imaging and PDT.

    2. Identification of Spermidine Binding Site in T-box Riboswitch Antiterminator RNA

      Jia Liu, Chunxi Zeng, Vivian Hogan, Shu Zhou, Md Masud Monwar and Jennifer V. Hines

      Article first published online: 5 OCT 2015 | DOI: 10.1111/cbdd.12660

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      The T-box transcription antitermination riboswitch controls bacterial gene expression by structurally responding to uncharged, cognate tRNA, in part by base pairing with an antiterminator element within the riboswitch. Spermidine binds the T-box antiterminator RNA in a location important for antiterminator function. The implications of these findings are significant both for better understanding the T-box riboswitch mechanism and for antiterminator-targeted drug discovery efforts.

    3. Synthesis of Analogues of BCTC Incorporating a Pyrrolidinyl Linker and Biological Evaluation as Transient Receptor Potential Vanilloid 1 Antagonists

      Lin Yan, Jingjie Wang, Miaobo Pan, Qianqian Qiu, Wenlong Huang and Hai Qian

      Article first published online: 5 OCT 2015 | DOI: 10.1111/cbdd.12661

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      A series of novel pyrrolidinyl linker TRPV1 antagonists were prepared in an effort to lower the hyperthermic side-effects of first-generation antagonist BCTC. These compounds were investigated for antagonism of hTRPV1 activation by capsaicin and acid in vitro. Preliminary results suggested the compounds 10a, 10b, 10c and 10j had favorable TRPV1 antagonism activity. In further studies in vivo, 10b, comparable to BCTC, showed potent analgesic activity in capsaicin-induced and heat-induced pain models. In addition, 10b indicated a reduced risk of body temperature elevation. All of these demonstrated that 10b can be considered as a safe candidate for the further development of analgesic drugs.

    4. New Tacrine Hybrids with Natural-Based Cysteine Derivatives as Multitargeted Drugs for Potential Treatment of Alzheimer's Disease

      Rangappa S. Keri, Catarina Quintanova, Sílvia Chaves, Diana F. Silva, Sandra M. Cardoso and M. Amélia Santos

      Article first published online: 29 SEP 2015 | DOI: 10.1111/cbdd.12633

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      Tacrine-phytonutrient conjugates as anti-AD multitargeting agents for cholinergic recover and cellular neuroprotection.

    5. A Splicing Reporter Tuned to Non-AG Acceptor Sites Reveals that Luteolin Enhances the Recognition of Non-canonical Acceptor Sites

      Masanori Chiba, Hiroyoshi Ariga and Hiroshi Maita

      Article first published online: 29 SEP 2015 | DOI: 10.1111/cbdd.12656

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      To find compounds that restore splicing at the mutated acceptor site, we constructed a splicing reporter gene. Addition of a modified polypyrimidine tract to the reporter gene mediated splicing at adjacent non-canonical acceptor sites, including the original mutated site. Certain flavons such as luteolin and apigenin enhanced aberrant splicing at the original non-canonical acceptor site of the reporter gene.

    6. Design, Synthesis, and Biological Evaluation of Novel 2-(Pyridin-3-yloxy)acetamide Derivatives as Potential Anti-HIV-1 Agents

      Boshi Huang, Xiao Li, Peng Zhan, Erik De Clercq, Dirk Daelemans, Christophe Pannecouque and Xinyong Liu

      Article first published online: 29 SEP 2015 | DOI: 10.1111/cbdd.12657

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      Through a structure-based molecular hybridization and bioisosterism approach, a series of novel 2-(pyridin-3-yloxy)acetamide derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cell cultures. Preliminary structure–activity relationships (SARs) analysis was detailed, and molecular docking studies were also carried out to investigate the binding mode of the most potent inhibitor Ij in the binding pocket of HIV-1 RT.

  10. Research Letters

    1. Synthesis and Biological Evaluation of Novel FtsZ-targeted 3-arylalkoxy-2,6-difluorobenzamides as Potential Antimicrobial Agents

      Shengsheng Qiang, Changde Wang, Henrietta Venter, Xin Li, Yi Wang, Liwei Guo, Ruixin Ma and Shutao Ma

      Article first published online: 28 SEP 2015 | DOI: 10.1111/cbdd.12658

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      3-O-Chlorobenzyl and 3-O-methylbenzyl derivatives 36 and 41 exhibited the most potent cell division inhibitory activity and antibacterial activity against four phenotypes of Gram-positive strains including MRSA.

  11. Research Articles

    1. Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2

      Ignacio Delso, Jessika Valero-González, Eduardo Marca, Tomás Tejero, Ramón Hurtado-Guerrero and Pedro Merino

      Article first published online: 21 SEP 2015 | DOI: 10.1111/cbdd.12650

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      A series of docking-guided glycomimetics have been synthesized and evaluated by fluorescence spectroscopy and STD-NMR experiments. The studies revealed that a minimum of three glucose units linked via a β-(1,3) linkage are required for achieving molecular recognition at the binding donor site.

    2. Site-directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non-Nucleoside Inhibitors

      Lida Savi, Margherita Brindisi, Gloria Alfano, Stefania Butini, Valeria La Pietra, Ettore Novellino, Luciana Marinelli, Andrea Lossani, Federico Focher, Caterina Cavella, Giuseppe Campiani and Sandra Gemma

      Article first published online: 18 SEP 2015 | DOI: 10.1111/cbdd.12630

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      A novel allosteric site on human adenosine kinase (hAK) for pyrrolobenzoxa(thia)zepinone non-nucleoside inhibitors was hypothesized by us. Bioinformatics analysis led us to identify the key residues of the postulated site. We herein cloned and expressed specific, single and double point mutants of hAK. Gratifyingly, mutated enzymes show reduced susceptibility to our compounds, while maintaining comparable affinity for nucleoside inhibitors to the wild-type enzyme. This study represents the first characterization and validation of a novel allosteric site in hAK.

    3. Analysis of Enoyl-Acyl Carrier Protein Reductase Structure and Interactions Yields an Efficient Virtual Screening Approach and Suggests a Potential Allosteric Site

      Mohammad A. Ghattas, Ramez A. Mansour, Noor Atatreh and Richard A. Bryce

      Article first published online: 16 SEP 2015 | DOI: 10.1111/cbdd.12635

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      Analysis of 80 enoyl-acyl carrier protein reductase X-ray structures finds druggable pockets with diverse topology which subsequently influences virtual screening enrichment. A druggable proximal pocket in Plasmodium falciparum enoyl-acyl carrier protein reductase (pfFabI) is predicted that could potentially act as a binding site for allosteric inhibitors. Inclusion of pharmacophoric constraints based on 59 ligand/enoyl-acyl carrier protein reductase X-ray structures improves docking pose prediction and significantly enhances enrichment of virtual screens.

  12. Reviews

    1. Coumarin: A Privileged Scaffold for the Design and Development of Antineurodegenerative Agents

      Ehtesham Jameel, Tarana Umar, Jitendra Kumar and Nasimul Hoda

      Article first published online: 16 SEP 2015 | DOI: 10.1111/cbdd.12629

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      Coumarins are exemplary of an assorted and aptitudinally useful set of drugs. Their promising applications in the field of neurodegenerative medication are exemplified by clinical candidates such as nodakenin that have been potent for demoting memory impairment.

  13. Research Articles

    1. Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex

      William Schlecht, King-Lun Li, Dehong Hu and Wenji Dong

      Article first published online: 16 SEP 2015 | DOI: 10.1111/cbdd.12651

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      A fluorescence based method for rapid and thorough Ca2+ sensitizer characterization which monitors the state of cardiac troponin C's (cTnC's) hydrophobic cleft was developed and tested using four important cardiotonic agents, levosimendan, pimobendan, EMD 57033, and bepridil. The effects of each Ca2+ sensitizer on cTnC's Ca2+ sensitivity and relaxation kinetics were determined in the presence of various cTnC binding partners, which enabled a more thorough understanding of the mechanisms of action behind each drug.

    2. HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells

      Ewa Kozela, Christeene Haj, Lumir Hanuš, Mukesh Chourasia, Avital Shurki, Ana Juknat, Nathali Kaushansky, Raphael Mechoulam and Zvi Vogel

      Article first published online: 16 SEP 2015 | DOI: 10.1111/cbdd.12637

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      The study describes the synthesis and the anti-inflammatory activities of two derivatives of the non-psychoactive cannabinoid, cannabidiol (CBD): HU-446 and HU-465 ((−)- and (+)-8,9-dihydro-7-hydroxy-CBD, respectively). HU-446 is a derivative of the natural (−)-CBD with negligible affinity towards CB1 or CB2 receptors while HU-465, a derivative of synthetic (+)-CBD, is capable of interacting with both. HU-446 and HU-465 decrease the in vitro activation of encephalitogenic T cells by MOG35-55, including their proliferation and IL-17 release, a key autoimmune cytokine.

  14. Research Letters

    1. Synthesis and Biological Evaluation of Fluorinated 3-Phenylcoumarin-7-O-Sulfamate Derivatives as Steroid Sulfatase Inhibitors

      Sebastian Demkowicz, Mateusz Daśko, Witold Kozak, Katarzyna Krawczyk, Dariusz Witt, Maciej Masłyk, Konrad Kubiński and Janusz Rachon

      Article first published online: 14 SEP 2015 | DOI: 10.1111/cbdd.12652

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      In this paper, we report a convenient method for the synthesis and biological evaluation of fluorinated 3-phenylcoumarin-7-O-sulfamate derivatives exhibiting STS activity. Additionally, their binding modes have been modeled using docking techniques. New coumarin analogs occurred to be potent STS inhibitors and revealed promising activity in vitro.

  15. Research Articles

    1. Biotin/Folate-decorated Human Serum Albumin Nanoparticles of Docetaxel: Comparison of Chemically Conjugated Nanostructures and Physically Loaded Nanoparticles for Targeting of Breast Cancer

      Navid Nateghian, Navid Goodarzi, Mohsen Amini, Fatemeh Atyabi, Mohammad Reza Khorramizadeh and Rassoul Dinarvand

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12624

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      The aim of this study was to use the advantage of both EPR effect and active targeting of nanoparticles using targeting moieties to increase the specific uptake of the drug delivery system by cancer cells. The results showed that the antitumor effect of these conjugates was much greater than the free drug and survival time in longer as well. Thus, they might be promising drug delivery systems for cancer treatment which may develop their manufacturing method for large-scale production.

    2. Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents

      Hakan Göker, Cigdem Karaaslan, Mustafa Orhan Püsküllü, Sulhiye Yildiz, Yalcin Duydu, Aylin Üstündağ and Can Özgür Yalcin

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12623

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      A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized and evaluated for their in vitro antibacterial activity against MRSA (Compound 11, MIC values 0.19 μg/mL) and VRE (Compound 8, MIC values 1.56 μg/mL)

    3. New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata

      Thiago Belarmino de Souza, Keila Mercês de Oliveira Brito, Naiara Chaves Silva, Raissa Prado Rocha, Grasiely Faria de Sousa, Lucienir Pains Duarte, Luiz Felipe Leomil Coelho, Amanda Latércia Tranches Dias, Marcia Paranho Veloso, Diogo Teixeira Carvalho and Danielle Ferreira Dias

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12625

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      A new series of glucosides modified in their saccharide units were synthesized and evaluated against Candida sp. The benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (3-fold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. The selectivity index (32) suggests its potential as an agent to treat Candida glabrata infections.

  16. Reviews

    1. Considerations of Protein Subpockets in Fragment-Based Drug Design

      Matthew Bartolowits and V. Jo Davisson

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12631

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      Fragment based drug design continues to gain importance in the field of drug discovery, but gaps in the tools and methods available in the identification and accurate utilization of protein subpockets have limited the scope. This review examines current computational methods for identifying ligand binding sites and predicting binding site similarity. The importance of considering binding site microenvironments is discussed as well as the significance of inducible subpockets as ways to improve future computational screening and fragment based design approaches..

  17. Research Articles

    1. pLR-HL: A Novel Amphibian Bowman–Birk-type Trypsin Inhibitor from the Skin Secretion of the Broad-folded Frog, Hylarana latouchii

      Yan Lin, Haiying Hang, Tianbao Chen, Mei Zhou, Lei Wang and Chris Shaw

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12626

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      A Bowman-Birk-type trypsin inhibitor (pLR-HL) was identified from the skin secretion of the broad-folded frog, Hylarana latouchii. Substitution of Lys8 with Phe (Phe8-pLR-HL) resulted in elimination of trypsin inhibitory activity and emergence of chymotrypsin inhibitory activity. The disulphide loops of pLR-HL and Phe8-pLR-HL retained similar inhibitory potencies towards trypsin/chymotrypsin compared with the original intact molecules. Thus, replacement of reactive site residues could alter the specificity of these protease inhibitors, while the canonical reactive loop alone can independently constitute biologically-active moiety.

    2. Lentivirus-mediated RNA Interference Targeting LAPTM4B Inhibits Human Ovarian Cancer Cell Invasion In Vitro

      Fanling Meng, Xiuwei Chen, Hongtao Song, Ge Lou and Songbin Fu

      Article first published online: 31 AUG 2015 | DOI: 10.1111/cbdd.12632

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      Lysosomal-associated protein transmembrane 4 beta expression may be an oncogene-inducing feature of invasive ovarian cancer cells and may be a potential therapeutic target for ovarian cancer treatment.

    3. Design and Synthesis of Nicotinic Acetylcholine Receptor Antagonists and their Effect on Cognitive Impairment

      Pattaporn Jaikhan, Chantana Boonyarat, Kuntarat Arunrungvichian, Palmer Taylor and Opa Vajragupta

      Article first published online: 27 AUG 2015 | DOI: 10.1111/cbdd.12627

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      QN1 and BZ1 were identified by in silico target based design for cognitive impairments. QN1 and BZ1 were found to be antagonists at the α4β2 nicotinic acetylcholine receptor and improved learning and memory deficits in amnesia mice models.

  18. Research Letters

    1. Screening and Identification of Inhibitors of Trypanosoma brucei Cathepsin L with Antitrypanosomal Activity

      Tierra Jefferson, Danielle McShan, Jasmine Warfield and Ifedayo Victor Ogungbe

      Article first published online: 27 AUG 2015 | DOI: 10.1111/cbdd.12628

      Thumbnail image of graphical abstract

      The major cathepsin L (rhodesain) in T. brucei have long been shown as a good and druggable target for new antitrypanosomal drugs. We report in this article compounds that can be optimized and developed as drug leads against trypanosomiasis in a structure-based approach using rhodesain.


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