Chemical Biology & Drug Design

Cover image for Vol. 83 Issue 4

Accepted Articles (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Edited By: David Selwood

Impact Factor: 2.469

ISI Journal Citation Reports © Ranking: 2012: 27/59 (Chemistry Medicinal); 176/290 (Biochemistry & Molecular Biology)

Online ISSN: 1747-0285

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  1. Research Articles

    1. Design, synthesis and biological evaluation of peptidyl epoxyketone proteasome inhibitors composed of β-amino acids

      Jiankang Zhang, Mengmeng Han, Xiaodong Ma, Lei Xu, Jiayi Cao, Yubo Zhou, Jia Li, Tao Liu and Yongzhou Hu

      Accepted manuscript online: 18 APR 2014 03:18AM EST | DOI: 10.1111/cbdd.12342

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      A series of novel di- and tripeptidyl epoxyketone derivatives, as exemplified by compounds 21d and 21e, were designed, synthesized and evaluated as proteasome inhibitors. The experimental results validated that the β-amino acid building block is potential for the development of proteasome inhibitors.

    2. Structure Activity Relationships for a Series of Compounds that Inhibit Aggregation of the Alzheimer's Peptide, Aβ42

      Angela Fortner McKoy, Jermont Chen, Trudi Schupbach and Michael H. Hecht

      Accepted manuscript online: 18 APR 2014 03:18AM EST | DOI: 10.1111/cbdd.12341

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      Eleven analogues of a novel inhibiter of Aβ42 aggregation (D737) were tested. Overall, the ability of a compound to inhibit Aβ aggregation was a good predictor of its ability to reduce Aβ induced cell toxicity and prolong the lifespan and locomotive ability of the transgenic fly model for Alzheimer's disease.

    3. Design, Synthesis, Anti-Tobacco Mosaic Virus (TMV) Activity and SARs of 7-Methoxycryptopleurine Derivatives

      Ziwen Wang, Anzheng Feng, Mingbo Cui, Yuxiu Liu, Lizhong Wang and Qingmin Wang

      Accepted manuscript online: 18 APR 2014 03:18AM EST | DOI: 10.1111/cbdd.12340

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      A series of 7-methoxycryptopleurine derivatives 223 were prepared and first evaluated for their antiviral activity. Most of these compounds exhibited excellent anti-TMV activity, especially for 16, 19 and 23.

    4. Synthesis and Anti-tubercular screening of [(2-chloroquinolin-3-yl)methyl] thiocarbamide derivatives.

      Suresh Kumar, Neeraj Upmanyu, Obaid Afzal and Sandhya Bawa

      Accepted manuscript online: 18 APR 2014 03:18AM EST | DOI: 10.1111/cbdd.12339

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      A series of quinoline thiocarbamide derivatives as structural analogues of Ethionamide were synthesized and screened against Mycobacterium tuberculosis (ATCC-25177). Compound having two halogens in the phenyl rings viz. 3g, 3h, 4g and 4h exhibited MIC of 50 μg/mL.

    5. Multi-objective Optimization on Anti-platelet Effects of Three-Components Combination by Quantitative Composition-activity Relationship Modeling and Weighted-Sum Method

      Yi Huang, Wei Jiang, Yang Xiao, Yi Wang and Yi Wang

      Accepted manuscript online: 12 APR 2014 04:50AM EST | DOI: 10.1111/cbdd.12338

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      We proposed a multi-objective optimization approach by QCAR modeling coupled with weighted sum method to search the optim al combination among three-com- onents on anti-platelet effect ass-ay in three aggregation agents. The combination set was evaluated and validated to prove the rationality of this approach.

    6. Synthesis, Molecular Docking and Biological Evaluation of Some Novel Hydrazones and Pyrazole Derivatives as Anti-inflammatory Agents

      Khaled Omar Mohammed and Yassin Mohammed Nissan

      Accepted manuscript online: 10 APR 2014 10:57AM EST | DOI: 10.1111/cbdd.12336

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      The research describes the synthesis and molecular docking of novel anti-inflammatory agents and their biological evaluation including serum PGE2 inhibition as well as COX-1 and COX-2 inhibition activity.

    7. Synthesis and evaluation of antimalarial properties of novel 4-aminoquinoline hybrid compounds

      Gillian M Fisher, Rajendra P. Tanpure, Antoine Douchez, Katherine T Andrews and Sally-Ann Poulsen

      Accepted manuscript online: 10 APR 2014 10:56AM EST | DOI: 10.1111/cbdd.12335

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      The chlorinated 4-aminoquinoline scaffold is the core structure of chloroquine, an established antimalarial drug, while the primary sulfonamide group has a track record of efficacy and safety in many clinically used drugs and was recently shown to exhibit antimalarial activity. Pharmacophore hybridization to generate novel 7-chloro-4-aminoquinoline:primary sulfonamide hybrid antimalarial compounds was investigated. The hybrid compounds had lower antimalarial activity when compared to chloroquine, however they demonstrated a number of interesting structure-activity relationship trends including the potential to overcome the resistance profile of chloroquine.

    8. Molecular dynamics of interactions between rigid and flexible antifolates and dihydrofolate reductase from pyrimethamine-sensitive and –resistant Plasmodium falciparum

      Wanwimon Mokmak, Surasak Chunsrivirot, Supa Hannongbua, Yongyuth Yuthavong, Sissades Tongsima and Sumalee Kamchonwongpaisan

      Accepted manuscript online: 9 APR 2014 08:30AM EST | DOI: 10.1111/cbdd.12334

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      To elucidate factors contributing to different binding affinities of pyrimethamine (PYR)/ WR99210 (WR) to wild type (WT) and quadruple mutant (QM) of dihydrofolate reductase of Plasmodium falciparum (PfDHFR), we performed molecular simulations on the WR-WT, WR-QM, PYR-WT, and PYR-QM complexes and found that Ile14 and Asp54 were crucial for binding of PYR/WR to PfDHFR. The quadruple mutations caused PYR to substantially lose hydrogen bond occupation percentages to Ile14 and Leu164, and to be displaced from its optimal orientation for Asp54 interaction.

  2. Research Letters

    1. Novel fluorescently labeled peptide compounds for detection of oxidized low-density lipoprotein at high specificity

      Akira Sato, Hikaru Yamanaka, Keitato Oe, Yoji Yamazaki and Keiichi Ebina

      Accepted manuscript online: 9 APR 2014 08:30AM EST | DOI: 10.1111/cbdd.12333

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      The probes for specific detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to be useful for the identification, diagnosis, prevention, and treatment of atherosclerosis. We developed two fluorescein isothiocyanate (FITC)-labeled peptide compounds— (FITC)KP6 and (FITC-AC)KP6— bound with high specificity to ox-LDL in a dose-dependent manner. These compounds may be effective novel fluorescent probes for specific detection of ox-LDL.

  3. Research Articles

    1. Identification of novel inhibitors of Daboia ruselli phospholipase A2 using the combined pharmacophore modeling approach

      Ramakrishnan C, Vikram Joshi, Joseph J.M, Vishwanath B. S and Velmurugan D

      Accepted manuscript online: 7 APR 2014 03:03AM EST | DOI: 10.1111/cbdd.12332

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      Four new viper phospholipaseA2 inhibitors were selected based on pharmacophore based virtual screening, docking, MD simulation and MM-GB/SA methods. Biochemical assay confirms that two compounds inhibit viper sPLA2 and the other two compounds inhibit structurally similar sPLA2 from Naja naja snake venom.

    2. Synthesis, characterization, and In vitro studies of PLGA-PEG nanoparticles for oral Insulin delivery

      Sara Hosseininasab, Roghiyeh Pashaei-Asl, Amir Ahmad Khandaghi, Hamid Tayefi Nasrabadi, Kazem Nejati-Koshki, Abolfazl Akbarzadeh, Sang Woo Joo, Younes Hanifehpour and Soodabeh Davaran

      Accepted manuscript online: 31 MAR 2014 03:10AM EST | DOI: 10.1111/cbdd.12318

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      The drug release study from PLGA– PEG copolymers nanoparticles was carried out in various pHs medium. As figure indicated, cumulative amount of insulin release was measured at pH 2.5 (similar the pH environment before meal in the stomach), 6.6, and 7.4 (simulating the pH environment in the intestine).

    3. Identification of Dipeptidyl Peptidase IV Inhibitors: Virtual Screening, Synthesis and Biological Evaluation

      Junhao Xing, Qing Li, Shengping Zhang, Haomiao Liu, Leilei Zhao, Haibo Cheng, Yuan Zhang, Jinpei Zhou and Huibin Zhang

      Accepted manuscript online: 27 MAR 2014 02:16PM EST | DOI: 10.1111/cbdd.12327

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      Several compounds with Tetrahydroisoquinoline scaffold were identified by multi-stage virtual screening as the antidiabetic drugs candidates against DPP-4.

    4. Mannosylated N-Aryl Substituted 3-Hydroxypyridine-4-ones:Synthesis, Hemagglutination Inhibitory Properties and Molecular Modeling

      Željka Car, Tomica Hrenar, Vesna Petrović Peroković, Rosana Ribić, Mateja Seničar and Srđanka Tomić

      Accepted manuscript online: 26 MAR 2014 10:29AM EST | DOI: 10.1111/cbdd.12329

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      We prepared mannosylated N-aryl substituted 3-hydroxypyridine-4-ones and explored their hemagglutination inhibitory properties as a FimH antagonists. Molecular modeling studies revealed the specific interactions with the FimH residues providing possible explanation for the observed inhibition.

    5. Synthesis and Anti-HIV Activity of 4-(Naphthalen-1-yl)-1,2,5-thiadiazol-3- hydroxyl Derivatives

      Diwakar Rai, Wenmin Chen, Peng Zhan, Hong Liu, Ye Tian, Xin Liang, Erik De Clercq, Christophe Pannecouque, Jan Balzarini and Xinyong Liu

      Accepted manuscript online: 26 MAR 2014 10:28AM EST | DOI: 10.1111/cbdd.12328

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      Biological results showed that compound Ih displayed moderate inhibitory activity against wild-type (wt) HIV-1 replication with EC50 values ranging from 16 µM. Molecular docking of compound Ih with wt HIV-1 RT was performed to understand the binding mode between these inhibitors and the wt HIV-1 RT and to rationalize some SARs.

    6. Structure-function relationship of Val/Arg-rich peptides: effects of net charge and Pro on activity

      QQ Ma, WJ Jiao, YF Lv, N Dong, X Zhu and AS Shan

      Accepted manuscript online: 20 MAR 2014 01:40PM EST | DOI: 10.1111/cbdd.12325

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      A new series of analogs of Val/Arg-rich peptides were designed to investigate the effect of net charge and position on activity. The substitution of Gly with Pro significantly decreased the toxicity The Increase of net charge from +4 to +6 significantly improved antimicrobial activity and decreased the toxicity against red blood cells. However antibacterial and hemolytic activities were not affected by increasing and net charge from + to +8 ,indicating a moderate net positive charge.

    7. Rational Design and Screening Study of Novel Lead Compound Based on Acetohydroxyacid Synthase Structure

      Jingnan Jin, Xiaojuan Qi, Dandan Yao, Bangqiang Mao, Jianhong Li, Qingye Zhang and Changshui Chen

      Accepted manuscript online: 18 MAR 2014 07:22AM EST | DOI: 10.1111/cbdd.12320

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      Lead compound with IC50 value of 47.41mg/L was screened out based on AHAS target.

      Optimization and syntheses of lead compound were performed and the inhibition rates of the synthesized compound increased by 30%-50%.

      The possible inhibitory mechanisms were analyzed by molecular docking.

    8. 1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for Phospholipase D

      Aditya Kulkarni, Phong Quang, Victoriana Curry, Renee Keyes, Weihong Zhou, Hyejin Cho, Jonathan Baffoe, Béla Török and Kimberly Stieglitz

      Accepted manuscript online: 18 MAR 2014 07:22AM EST | DOI: 10.1111/cbdd.12319

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      This study reports synthesis of a new class of PLD inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure. These molecules exhibited inhibition of human recombinant PLD activity (IC50) in the low nanomolar to low micromolar range with monomeric substrate diC4PC and phospholipid vesicles and micelles. Preliminary activity studies using recombinant human PLDs in in-vivo cell assays measuring both transphosphatidylation and head group cleavage indicates inhibition in the mid to low nanomolar range for these potent inhibitory novel molecules in a physiological environment.

    9. Synthesis and biological evaluation of substituted 5-methyl-2-phenyl-1H-pyrazol-3(2H)-one derivatives as selective COX-2 inhibitors: Molecular docking study

      Pritam N. Dube, Shweta S. Bule, Santosh N. Mokale, M. R. Kumbhare, P. R. Dighe and Y. V. Ushir

      Accepted manuscript online: 18 MAR 2014 04:55AM EST | DOI: 10.1111/cbdd.12324

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      A series of pyrazolone derivatives were prepared and evaluated for their anti-inflammatory activities and selectivity as COX-2 inhibitor. The derivatives were further evaluated for antioxidant activity.

    10. Microwave Assistant One Pot Synthesis, Crystal Structure, Antifungal Activities and 3D-QSAR of Novel 1,2,4-Triazolo[4,3-a]pyridines

      Xing-Hai Liu, Zhao-Hui Sun, Ming-Yan Yang, Cheng-Xia Tan, Jian-Quan Weng, Yong-Gang Zhang and Yi Ma

      Accepted manuscript online: 18 MAR 2014 04:55AM EST | DOI: 10.1111/cbdd.12323

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      A series of novel 1,2,4-triazolo[4,3-a]pyridines were synthesized. The antifungal activity results indicated that the compound 2b, 2g, 2p, 2i exhibited good activities. The activity of compound 2b, 2g, 2p, 2i can compare with the commercial pesticide. The 3D-QSAR model was developed using CoMFA method

    11. Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: the effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity

      Nenad Filipović, Sonja Grubišić, Maja Jovanović, Marija Dulović, Ivanka Marković, Olivera Klisurić, Aleksandar Marinković, Dragana Mitić, Katarina Anđelković and Tamara Todorović

      Accepted manuscript online: 18 MAR 2014 04:55AM EST | DOI: 10.1111/cbdd.12322

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      The effect of the chelate ring size and complex lipophilicity on in vitro cytotoxic activity of Pd(II) complexes with NN bidentate N-heteroaromatic hydrazones was investigated. It was shown that more lipophilic complexes with quinoline backbone were more potent in the cytotoxic action than pyridine analogues. The cytotoxicity of most efficient novel Pd(II) complex 1 is comparable to the activity of cisplatin in all cell lines investigated, and is predominantly mediated through induction of apoptotic cell death.

    12. Proteomic Analysis of Proteins Engaged in α-Methylene-δ-Lactone Cytotoxic Effects in Hormone-Independent Breast Cancer MDA-MB-231 Cells

      Anna Wyrebska, Zofia Pawlowska, Katarzyna Gach, Piotr Komorowski, Anna Protas, Bogdan Walkowiak and Anna Janecka

      Accepted manuscript online: 11 MAR 2014 12:10PM EST | DOI: 10.1111/cbdd.12317

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      The protein expression profiles were investigated in MDA-MB-231 breast cancer cells exposed to a synthetic α-methylene-δ-lactone, 1-isopropyl-2-methylene-1,2-dihydrobenzochromen-3-one, designated DL-3. Using the 2D gel electrophoresis, a set of eight differentially expressed proteins were found and successfully identified by mass spectrometry (MALDI-TOF/MS). The proteomic results indicated new directions for the further studies of the pathways engaged in the anticancer action exerted by α-methylene-δ-lactones in cancer cells.

    13. Evaluation of anti-inflammatory and analgesic effects of synthesized derivatives of ibuprofen

      Jingjie Wang, Dongyan Dai, Qianqian Qiu, Xin Deng, Haiyan Lin, Hai Qian and Wenlong Huang

      Accepted manuscript online: 11 MAR 2014 12:09PM EST | DOI: 10.1111/cbdd.12316

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      A series of piperazine carboxamide, propanamide and pyrrolidine carboxamide derivatives of ibuprofen were designed by modifying carboxylic acid group of ibuprofen based on the common structure of transient receptor potential vanilloid type 1 (TRPV1) antagonists and synthesized. They were evaluated for cyclooxygenase inhibition, TRPV1 antagonistic, anti-inflammatory, analgesic, ulcerogenic action, and the effect on body temperature. Compound 17 emerged as a safe alternative analgesic candidate for pain treatment.

    14. In silico characterization of an atypical MAPK phosphatase of Plasmodium falciparum as a suitable target for drug discovery

      Christopher O. Campbell, Daniel N. Santiago, Wayne C. Guida, Roman Manetsch and John H. Adams

      Accepted manuscript online: 8 MAR 2014 01:42AM EST | DOI: 10.1111/cbdd.12315

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      Forward genetic analysis of Plasmodium falciparum identified an atypical MAPK phosphatase expressed from PF3D7_1305500 as an important for intraerythrocytic development. A homology model of the DUSP domain was used in high-throughput in silico screening of the available library of antimalarial compounds from ChEMBL-NTD and three had reduced activity against a ∆PF3D7_1305500 parasite, suggesting PF3D7_1305500 is a potential target of the selected compounds. Our data suggest that the atypical MAPK phosphatase represents a potentially new type of P. falciparum drug target.

    15. New Force Field on Modeling Intrinsically Disordered Proteins

      Wei Wang, Wei Ye, Cheng Jiang, Ray Luo and Hai-Feng Chen

      Accepted manuscript online: 4 MAR 2014 07:28AM EST | DOI: 10.1111/cbdd.12314

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      Two IDPs tests show that new force field of ff99IDPs has better character to model IDPs than ff99SBildn. The correlations between predicted secondary chemical shift and the corresponding experimental data for free MeV NTAIL protein under ff99IDPs force field driving MD simulations of free MeV NTAIL protein are 0.79, higher than that of ff99SBildn.

    16. Immunocompatibility and Toxicity Studies of Poly-L-Lysine Nanocapsules in Sprague Dawely Rats for Drug Delivery Applications

      P.A Janeesh, Haider Sami, C.R Dhanya, Sri Sivakumar and Annie Abraham

      Accepted manuscript online: 3 MAR 2014 04:04AM EST | DOI: 10.1111/cbdd.12313

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      PLL nanocapsules were synthesised by LbL approach and characterised by SEM microscopy and found to be 360nm in size. In vivo toxicity markers activity, haematological parameters alteration, RT-PCR analysis of important genes and immunoblotting showed least changes when compared with Group I and II. The result of our study provides the infromation about the immunocompatibility and nontoxicity of PLL nanocapsules for drug delivery applications in vivo.

    17. Design, synthesis and preliminary cardioprotective effect evaluation of Danshensu derivatives

      Qingbin Cui, Yonghong Chen, Mingjuan Zhang, Luchen Shan, Yewei Sun, Pei Yu, Gaoxiao Zhang, Dingyuan Wang, Zengchao Zhao, Qian Xu, Benhong Xu and Yuqiang Wang

      Accepted manuscript online: 3 MAR 2014 04:04AM EST | DOI: 10.1111/cbdd.12312

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      A serial of new Danshensu derivatives were synthesized and their cardioprotective effects were evaluated. Compound 14 exhibited much improved activity than Danshensu against tert-butyl hydroperoxide induced injury to cell and in the rat model of myocardial ischemia.

    18. Study of Orientation and Penetration of LAH4 into Lipid Bilayer Membranes: pH and Composition Dependence

      Matin Islami, Faramarz Mehrnejad, Farahnoosh Doustdar, Masumeh Alimohammadi, Mahmoud Khadem-Maaref, Mohammad Mir-Derikvand and Majid Taghdir

      Accepted manuscript online: 3 MAR 2014 04:04AM EST | DOI: 10.1111/cbdd.12311

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      In this study, we have performed MD simulations to compare LAH4 effects on anionic POPG bilayer and zwitterionic POPC bilayer. The peptide preferentially interacts with anionic membranes. Our data show that electrostatic interactions between His11 and the phosphor atoms of bilayers should have a significant impact on the penetration of LAH4.

    19. Peptide Inhibitors against Dengue Virus Infection

      Aussara Panya, Kunan Bangphoomi, Kiattawee Choowongkomon and Pa-thai Yenchitsomanus

      Accepted manuscript online: 26 FEB 2014 12:52AM EST | DOI: 10.1111/cbdd.12309

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      A short anti-dengue virus (DENV) peptide targeting to the hydrophobic pocket of DENV envelop protein was identified by molecular docking. The di-peptide, EF, was the most effective on DENV2 infection inhibition in vitro. This result provides the proof-of-concept for development of therapeutic peptide inhibitors against DENV infection by the computer-aided molecular design.

    20. Synthesis of novel heterocyclic ring-fused 18β-glycyrrhetinic acid derivatives with antitumor and antimetastatic activity

      Cheng Gao, Fu-Jun Dai, Hai-Wei Cui, Shi-Hong Peng, Yuan He, Xue Wang, Zheng-Fang Yi and Wen-Wei Qiu

      Accepted manuscript online: 26 FEB 2014 12:52AM EST | DOI: 10.1111/cbdd.12308

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      By introducing various five-member fused heterocyclic rings at C-2 and C-3 positions, 18 novel GA derivatives were obtained. These compounds were evaluated for their inhibitory activity against the growth of 8 different tumor cell lines using a SRB assay. The most active compound 37 was about 11-fold more potent than GA on antiproliferative activity and was about 20-fold more potent than GA on antimetastatic activity.

    21. Discovery of Novel Secretory Phospholipase A2 Inhibitors Using Virtual Screen

      Shunchen Qiu, Fangjin Chen, Ying Liu and Luhua Lai

      Accepted manuscript online: 26 FEB 2014 12:51AM EST | DOI: 10.1111/cbdd.12307

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      Through structure-based virtual screen, Fmoc-phenylalanine derivatives and azo derivatives have been identified as two new types of hnpsPLA2 inhibitors, which may serve as novel scaffolds for developing potent hnpsPLA2 inhibitors. These compounds bind to hnpsPLA2 by interacting with the catalytic calcium ion and the hydrophobic regions in the substrate binding pocket.

    22. Modeling The Met-Form Of Human Tyrosinase: A Refined And Hydrated Pocket For Antagonist Design

      Elisabeth Favre, Antoine Daina, Pierre-Alain Carrupt and Alessandra Nurisso

      Accepted manuscript online: 24 FEB 2014 12:12PM EST | DOI: 10.1111/cbdd.12306

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      A robust homology model of human Tyrosinase was built by using structural information from Streptomyces castaneoglobisporus tyrosinase and Ipomea batata catecholoxidase enzymes. Structural water molecules were identified through the analysis of the available crystallographic structures of tyrosinases from other species. Phenylthiourea (PTU), a tyrosinase inhibitor, docked into the solvated human active pocket, revealed a binding mode consistent with crystallographic information, highlighting the reliability of the model.

    23. Site-Specific Labeling of Proteins and Peptides with Trans-cyclooctene Containing Handles Capable of Tetrazine Ligation

      James W. Wollack, Benjamin J. Monson, Jonathan K. Dozier, Joseph J. Dalluge, Kristina Poss, Scott A. Hilderbrand and Mark D. Distefano

      Accepted manuscript online: 22 FEB 2014 09:54AM EST | DOI: 10.1111/cbdd.12303

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      A trans-cyclooctene containing PFTase substrate was synthesized in six steps from geraniol. This substrate was enzymatically transferred to proteins and peptides ending a “CAAX” motif. After enzymatic labeling these proteins and peptides were subsequently targeted by tetrazines using an inverse-electron-demand Diels-Alder reaction.

    24. Computer-aided Discovery of Trypanosoma brucei RNA-editing Terminal Uridylyl Transferase 2 Inhibitors

      Özlem Demir, Mehdi Labaied, Chris Merritt, Ken Stuart and Rommie E. Amaro

      Accepted manuscript online: 22 FEB 2014 09:28AM EST | DOI: 10.1111/cbdd.12302

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      TbRET2 is an indispensable enzyme for Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT), and is targeted using a computational approach that combines molecular dynamics simulations and virtual screening. The compounds prioritized are then tested in T. brucei via Alamar blue cell viability assays. This work identified 20 drug-like compounds which are candidates for further testing in the drug discovery process.

    25. Discovery of Novel P-Glycoprotein-Mediated Multidrug Resistance Inhibitors Bearing Triazole Core via Click Chemistry

      Baomin Liu, Qianqian Qiu, Tianxiao Zhao, Lei Jiao, Jianyu Hou, Yunman Li, Hai Qian and Wenlong Huang

      Accepted manuscript online: 20 FEB 2014 04:16AM EST | DOI: 10.1111/cbdd.12301

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      A novel class of P-gp-mediated MDR inhibitors were designed, synthesized and evaluated for their reversal activity. Compound 5 with lower cytotoxicity, higher reversal activity and long duration of effect was identified as a promising candidate for MDR inhibitor.

  4. Research Letters

    1. Discovery of the highly potent fluoroquinolone based benzothiazolyl-4-thiazolidinone hybrids as Antibacterials

      Rahul V. Patel and Se Won Park

      Accepted manuscript online: 13 FEB 2014 01:46PM EST | DOI: 10.1111/cbdd.12299

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      A truly rationalized design of a new class of 4-thiazolidinones revealed potent antibacterial efficacies with lowest MICs 1-2 µg/mL when compared to control drug ciprofloxacin at 3.12-6.25 µg/mL. Combination of electron withdrawing substituent on the benzothiazole ring and norfloxacin entity furnished anti Gram-positive effects as well as combination of electron releasing substituent with ciprofloxacin entity furnished anti Gram-negative potency. Two thiazole rings positively enhanced the potency of the final scaffolds.

  5. Research Articles

    1. In Vitro Evaluation Of Doxorubicin Incorporated Magnetic Albumin Nanospheres

      Ayça Zeybek, Gülşah Şanlı-Mohamed, Güliz Ak, Habibe Yılmaz and Şenay Hamarat Şanlıer

      Accepted manuscript online: 13 FEB 2014 12:44PM EST | DOI: 10.1111/cbdd.12300

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      In this study we found that M-DOX-BSA-NPs provide many advantages as targeted drug delivery, enhanced drug killing ability and bioavailability based on cytotoxicity, flow cytometry and confocal microscopy image results.

    2. Computational inhibition studies of the human proteasome by argyrin-based analogues with subunit specificity

      Eriketi Z. Loizidou and Constantinos D. Zeinalipour-Yazdi

      Accepted manuscript online: 12 FEB 2014 11:47AM EST | DOI: 10.1111/cbdd.12298

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      Three-dimensional models of the humanized proteasome active sites β1, β2 and β5 were developed and used to study the subunit selectivity of proteasome inhibitors, argyrin A and F. Site specific interactions and a probability-based specificity parameter derived in this study adequately explained the different subunit selectivities that are observed for each analogue. Based on this model and on maximizing site specific interactions, two new argyrin analogues are proposed as selective inhibitors of the caspase-like (β1 site) activity.

    3. A facile one pot synthesis of 2-arylamino-5-aryloxylalkyl-1,3,4-oxadiazoles and their urease inhibition studies

      Tashfeen Akhtar, Muhammad Ashfaq Khan, Jamshed Iqbal, Peter G. Jones and Shahid Hameed

      Accepted manuscript online: 3 FEB 2014 05:36PM EST | DOI: 10.1111/cbdd.12297

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      One pot synthesis of substituted 1,3,4-oxadiazoles was successfully achieved. The synthesized compounds were found very potent inhibitors of ureas, besides exhibiting antibacterial activities.

    4. You have full text access to this OnlineOpen article
      A Bifurcated Proteoglycan Binding Small Molecule Carrier for siRNA delivery

      Matt Gooding, Derick Adigbli, A. W. Edith Chan, Roberta J. Melander, Alexander J. MacRobert and David L. Selwood

      Accepted manuscript online: 28 JAN 2014 08:05AM EST | DOI: 10.1111/cbdd.12295

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      A bifurcated guanidylated small molecule is modelled to access different clusters of sulphate esters in proteoglycans bound to the cell surface. Modular synthesis gives ready access to these molecules which have potential for the delivery of siRNA.

    5. Novel fragment-based QSAR modelling and combinatorial design of pyrazole derived CRK3 inhibitors as potent anti-leishmanials

      Sukriti Goyal, Jaspreet Kaur Dhanjal, Chetna Tyagi, Manisha Goyal and Abhinav Grover

      Accepted manuscript online: 22 JAN 2014 07:02AM EST | DOI: 10.1111/cbdd.12290

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      A novel fragment based QSAR model has been developed using 22 pyrazole derived compounds exhibiting inhibitory activity against Leishmanial CRK3. Based on the fragment-based QSAR model, a combinatorial library was generated and top two compounds were reported after predicting their activity. The analysis carried out in this study provides a substantial basis for consideration of the designed pyrazole-based leads as potent anti-leishmanial drugs.

    6. Unraveling the Role of Arg4 and Arg6 in the Auto-inhibition Mechanism of GSK3β from Molecular Dynamics Simulation

      Linkai Mou, Molin Li, Shaoyong Lu, Shuai Li, Qiancheng Shen, Jian Zhang, Chuangang Li and Xuefeng Lu

      Accepted manuscript online: 20 JAN 2014 08:39AM EST | DOI: 10.1111/cbdd.12286

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      MD simulations were utilized to unravel the role of Arg4 and Arg6 in the auto-inhibition mechanism of GSK3β.

    7. Synthesis of Ranolazine derivatives containing the (1S,4S)-2,5-diazabicyclo[2.2.1]heptane moiety and their evaluation as vasodilating agents

      Manuel López-Ortiz, Ivan Monsalvo, Cristina Paredes-Carbajal, Carlos Hernández-Díaz, Marcos Hernández-Rodríguez, Patricia Demare, Dieter Mascher and Ignacio Regla

      Accepted manuscript online: 20 JAN 2014 08:26AM EST | DOI: 10.1111/cbdd.12285

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      Two diazabicyclic analogues of Ranolazine, (S,S,S)-5 and (S,S,R)-5, and their epimeric mixture, showed a vasodilating effect significantly greater than Ranolazine. This vasodilating activity has two components, one of them endothelium-dependent, due to the release of NO, and the other one due to a direct effect on the vascular smooth muscle. In a manner similar to Ranolazine, [(S,S,S)(S,S,R)]-5 and (S,S,R)-5 induce the release of a prostanoid, whose vasoconstrictor effect is masked by the predominant vasodilation induced by these compounds.

    8. Probing the origin of structural stability of single and double stapled p53 peptide analogs bound to MDM2

      Zuojun Guo, Kristina Streu, Goran Krilov and Udayan Mohanty

      Accepted manuscript online: 13 JAN 2014 02:01AM EST | DOI: 10.1111/cbdd.12284

      Thumbnail image of graphical abstract

      The conformation and structural stability of single and double stapled all-hydrocarbon cross-linked p53 peptides in solution and when bound to MDM2 are investigated. The free energy released by displacing the hydration sites populating the staple binding pocket was determined. The order of the peptides from lowest to highest binding affinity as determined by potential of mean forces and weight-histogram analysis methods are in agreement with experimental data.

    9. The discovery of a novel and selective inhibitor of PTP1B over TCPTP: 3D QSAR pharmacophore modeling, Virtual Screening, Synthesis and Biological Evaluation

      Ying Ma, Yuan-Yuan Jin, Ye-Liu Wang, Run-Ling Wang, Xin-Hua Lu, De-Xin Kong and Wei-Ren Xu

      Accepted manuscript online: 13 JAN 2014 02:01AM EST | DOI: 10.1111/cbdd.12283

      Thumbnail image of graphical abstract

      The current manuscript describes for the first time a novel class of selective inhibitors of PTP1B over TCPTP by means of the powerful “3D-QSAR” technique. Our results further indicate that the new inhibitors hold high potential to become promising drug candidates for developing novel and powerful drugs for diabetes mellitus.

    10. Synthesis of new lipoic acid conjugates and evaluation of their free radical-scavenging and neuroprotective activities

      Maria Laura Bolognesi, Christian Bergamini, Romana Fato, Joël Oiry, Jean-Jacques Vasseur and Michael Smietana

      Accepted manuscript online: 13 JAN 2014 02:00AM EST | DOI: 10.1111/cbdd.12282

      Thumbnail image of graphical abstract

      A series of new lipoic acid derivatives has been synthesized and evaluated for their potential antioxidant and neuroprotective activities. Structure-activity relationship studies comparing lipoic acids derivatives and their corresponding reduced analogues revealed the importance of free thiol functions.

  6. Research Letters

    1. Bis (histidine) with N2 vehicle: - An important skeleton for MR / chelation therapy

      Pooja Srivastava, Anjani K Tiwari, Dipti Kakkar, Vikas Kumar and Anil K Mishra

      Accepted manuscript online: 13 JAN 2014 02:00AM EST | DOI: 10.1111/cbdd.12281

      Thumbnail image of graphical abstract

      Bis (histidine) ethylenediamine tetraacetic acid shows thermodynamic and kinetic stability for chelation as well as MR application as contrast agent. Further investigation may increase their specificity and pharmacokinetics before commercial exploitation.

  7. Research Articles

    1. Effects of Novel Diarylpentanoid Analogues of Curcumin on Secretory Phospholipase A2, Cyclooxygenases, Lipoxygenase and Microsomal Prostaglandin E Synthase-1

      Waqas Ahmad, Endang Kumolosasi, Ibrahim Jantan, Syed Nasir Abbas Bukhari and Malina Jasamai

      Accepted manuscript online: 9 JAN 2014 10:07AM EST | DOI: 10.1111/cbdd.12280

      Thumbnail image of graphical abstract

      A series of novel diarylpentanoid analogues of curcumin was synthesized by direct coupling of the appropriate aromatic aldehyde with three ketones namely cyclohexanone, acetone and cyclopentanone, under base catalyzed Claisen–Schmidt condensation reaction. These analogues were screened for their inhibitory effects on the activity of secretory phospholipase A2 (sPLA2), cyclooxygenases (COX), soyabean lipooxygenase (LOX) as well as microsomal prostaglandin E synthase-1 (mPGES-1) using in vitro assays.

  8. Research Letters

    1. In Search of Potent 5–HT6 Receptor Inverse Agonists

      Greg Hostetler, Derek Dunn, Beth Ann McKenna, Karla Kopec and Sankar Chatterjee

      Accepted manuscript online: 9 JAN 2014 10:07AM EST | DOI: 10.1111/cbdd.12279

      Thumbnail image of graphical abstract

      Based on “HTS-hit” compound 1a Ki=5.73 uM against h5-HT6), compound 9 (Ki=14 nM) was developed. Enantiomers of 9 (Ki of 7 nM vs.38 nM) displayed effect of chirality on potency.

  9. Research Articles

    1. Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities

      Nafees Ahmed, Keyur G. Brahmbhatt, Shabana I. Khan, Melissa Jacob, Babu L. Tekwani, Sudeep Sabde, Debashis Mitra, Inder Pal Singh, Ikhlas A. Khan and Kamlesh K. Bhutani

      Accepted manuscript online: 15 JUN 2012 11:37AM EST | DOI: 10.1111/j.1747-0285.2012.01427.x

  10. Research Letters

    1. Virtual and In vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against Xanthine oxidase and Cyclooxygenase-2 for gout treatment

      Yadi Li, Christopher M. Frenz, Zhiwen Li, Mianhua Chen, Yurong Wang, Fengjuan Li, Cheng Luo, Jian Sun, Lars bohlin, Zhenjing Li, Hua Yang and Changlu Wang

      Accepted manuscript online: 3 OCT 2011 03:42PM EST | DOI: 10.1111/j.1747-0285.2011.01248.x

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