Chemical Biology & Drug Design

Cover image for Vol. 88 Issue 2

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

Edited By: David Selwood

Impact Factor: 2.802

ISI Journal Citation Reports © Ranking: 2015: 26/59 (Chemistry Medicinal); 137/289 (Biochemistry & Molecular Biology)

Online ISSN: 1747-0285

VIEW

  1. 1 - 46
  1. Research Articles

    1. Predicting subtype selectivity of dopamine receptor ligands with three-dimensional biologically relevant spectrum

      Zheng-Kun Kuang, Shi-Yu Feng, Ben Hu, Dong Wang, Song-Bing He and De-Xin Kong

      Version of Record online: 29 JUL 2016 | DOI: 10.1111/cbdd.12815

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      We applied a novel molecular descriptor, three-dimensional biologically relevant spectrum (BRS-3D), in subtype selectivity prediction of dopamine receptor (DR) ligands. BRS-3D is calculated by superposing the objective compounds against 300 template ligands from sc-PDB; it can encode the ligand's multiple conformations into a similarity array. BRS-3D-based method provided a new strategy for the selectivity prediction of structurally diverse ligands.

  2. Original Research

    1. Biohydroxylation of 7-oxo-DHEA, a natural metabolite of DHEA, resulting in formation of new metabolites of potential pharmaceutical interest

      Alina Świzdor, Anna Panek and Natalia Milecka-Tronina

      Version of Record online: 29 JUL 2016 | DOI: 10.1111/cbdd.12813

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      New oxygenated metabolites of biologically active 7-oxo-DHEA were formed by fungal stereoselective hydroxylations by Syncephalastrum racemosum. The studies demonstrated that the obtained derivatives may be simultaneously the final metabolites of DHEA. The observed reactions suggested that this micro-organism contains enzymes exhibiting similar activity to those present in human cells. The resulting compounds can be considered as potential components of the eukaryotic, including human, metabolome.

  3. Research Articles

    1. Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently

      Ambily Nath Indu Viswanath, Seo Yun Jung, Eun Mi Hwang, Ki Duk Park, Sang Min Lim, Sun-Joon Min, Yong Seo Cho and Ae Nim Pae

      Version of Record online: 27 JUL 2016 | DOI: 10.1111/cbdd.12810

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      This study aimed to find novel chemotypes by pharmacophore and structure-based virtual screening forTREK1 channel blockers. Electrophysiological assay confirmed the TREK1 modulating activities of 11 virtual hit compounds, among these, NC30, significantly reduced the channel current with an IC50 of 4.7 μM.

    2. Design, synthesis, biological evaluation, NMR and DFT studies of structurally simplified trimethoxy benzamides as selective P-glycoprotein inhibitors: the role of molecular flatness

      Angela Stefanachi, Giuseppe Felice Mangiatordi, Piero Tardia, Domenico Alberga, Francesco Leonetti, Mauro Niso, Nicola Antonio Colabufo, Carlo Adamo, Orazio Nicolotti and Saverio Cellamare

      Version of Record online: 26 JUL 2016 | DOI: 10.1111/cbdd.12811

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      We designed new structurally simplified trimethoxy benzamides to detect the minimal molecular requirements for P-gp modulation. The proposed ligands were provided with a high efficiency and IC50 values in the low micromolar range. By employing DFT and NMR approaches, we found a clear rationale bridging molecular flatness and P-gp modulation.

    3. Identification of CYP1B1-specific candidate inhibitors using combination of in silico screening, integrated knowledge-based filtering, and molecular dynamics simulations

      Rakesh Kumar and Dinesh Gupta

      Version of Record online: 21 JUL 2016 | DOI: 10.1111/cbdd.12803

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      The known inhibitors except in polycyclic aromatic hydrocarbons and selected ligands derived from docking of CYP1B1 is found to be at a optimum distance 6 Å of heme (Fe) to nearest non-hydrogen atom. The Cluster 1 was largest one containing 94 compounds using LibMCS classification. ∆Evdw component played dominant role in deciding binding energies of ligands, ∆Eele component supported in some ligands. The residues Ser131, Asp326, Asp333, and Thr510 were frequently involved in hydrogen bond formation in CYP1B1 interactions with ligands.

  4. Review Articles

    1. Multitargeted bioactive ligands for PPARs discovered in the last decade

      Jun Zhang, Xin Liu, Xian-Bin Xie, Xian-Chao Cheng and Run-Ling Wang

      Version of Record online: 21 JUL 2016 | DOI: 10.1111/cbdd.12806

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      In this review, we updated and generalized the recent development of PPARγ partial agonists, PPARγ antagonists, PPARα/γ dual agonists, PPARδ partial agonists, PPARδ antagonists, PPARα/δ dual agonists, PPARγ/δ dual agonists, and PPARα/γ/δ pan-agonists published in recent decade. Most of these molecules were modified from known structures or came from high-throughput screening.

  5. Research Articles

    1. Evaluation of the inhibitory activity of (aza)isoindolinone-type compounds: toward in vitro InhA action, Mycobacterium tuberculosis growth and mycolic acid biosynthesis

      Aurélien Chollet, Jean-Luc Stigliani, Maria Rosalia Pasca, Giorgia Mori, Christian Lherbet, Patricia Constant, Annaïk Quémard, Jean Bernadou, Geneviève Pratviel and Vania Bernardes-Génisson

      Version of Record online: 16 JUL 2016 | DOI: 10.1111/cbdd.12804

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      The pharmacomodulation and the synthesis of 15 new (aza)isoindolinone-type compounds were described. Two of them were more effective InhA inhibitors than the hit molecule. The modes of interaction of the (aza)isoindolinones with this enzyme were predicted based on molecular docking calculations and on the structure–activity relationship analysis. The (aza)isoindolinone exhibited only a discrete inhibitory activity upon M. tuberculosis H37Rv growth. Compounds m-4a and 2a were not able to inhibit the biosynthesis of mycolic acids.

    2. Cardioprotective effect of novel sulphonamides-1,3,5-triazine conjugates against ischaemic–reperfusion injury via selective inhibition of MMP-9

      Xiao-Zhu Zheng, Jia-Li Zhou, Jing Ye, Pei-Pei Guo and Chun-Shui Lin

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/cbdd.12807

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      Novel class of sulphonamides-1,3,5-triazine conjugates have been synthesized and tested for inhibitory activity against MMP-2 and MMP-9.

    3. 4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives as novel non-nucleoside agonists for the adenosine A1 receptor

      Barbara Cosimelli, Giovanni Greco, Sonia Laneri, Ettore Novellino, Antonia Sacchi, Maria Letizia Trincavelli, Chiara Giacomelli, Sabrina Taliani, Federico Da Settimo and Claudia Martini

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/cbdd.12801

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      We describe the biological characterization of two novel non-nucleoside agonists of the human A1 adenosine receptor. The two compounds are 4-amino-6-alkyloxy-2- alkylthiopyrimidine derivatives provided with submicromolar potency at the target receptor and high selectivity versus A2A, A2B and A3 adenosine receptors.

    4. An antiarrhythmic agent as a promising lead compound for targeting the hEAG1 ion channel in cancer therapy: insights from molecular dynamics simulations

      Daniel Șterbuleac and Călin Lucian Maniu

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/cbdd.12797

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      This study investigates the potential of using clofilium as a lead compound for finding a novel cancer therapy agent which may target the hEAG1 ion channel over hERG. The implied findings from a comparative assessment of literature studies were verified using molecular dynamics simulations. The results indicate a particular structural difference between hEAG1 and hERG channels that could provide a novel and realistic way of using clofilium analogues to target hEAG1 in cancer therapy.

    5. Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives

      Nina Božinović, Sandra Šegan, Sandra Vojnovic, Aleksandar Pavic, Bogdan A. Šolaja, Jasmina Nikodinovic-Runic and Igor M. Opsenica

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/cbdd.12809

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      A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Thiepine 8-phenyl[1]benzothiepino[3,2-c]pyridine efficiently killed Candida albicans at 15.6 µg/mL and showed no embryotoxicity at 75 µg/mL. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.

    6. Structure–activity relationship studies of benzyl-, phenethyl-, and pyridyl-substituted tetrahydroacridin-9-amines as multitargeting agents to treat Alzheimer's disease

      Wesseem Osman, Tarek Mohamed, Victor Munsing Sit, Maryam S. Vasefi, Michael A. Beazely and Praveen P. N. Rao

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/cbdd.12800

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      Anti-Alzheimer's agents with potent cholinesterase and beta-amyloid aggregation inhibition were identified. Tetrahydroacridin-9-amine derivatives with nanomolar-scale inhibition of both acetyl- and butyrylcholinesterase were discovered. A 3,4-dimethoxyphenyl substituent was identified as an antiamyloid pharmacophore.

    7. Design, synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring

      Jian Luo, Qiu-E Yang, Yuan-Yuan Yang, You-Zhi Tang and Ya-Hong Liu

      Version of Record online: 9 JUL 2016 | DOI: 10.1111/cbdd.12799

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      Through structure-based bioisosteric replacement, a series of novel piperazinesubstituted pleuromutilin derivatives were designed, synthesized. The antibacterial of these derivatives were evaluated. Three of these derivatives were selected for molecular docking investigations.

    8. Novel taxane derivatives from Taxus wallichiana with high anticancer potency on tumor cells

      Yong Wang, Jiaying Wang, Hao Wang and Wencai Ye

      Version of Record online: 6 JUL 2016 | DOI: 10.1111/cbdd.12782

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      In this work, we find four novel taxane derivatives with encouraging anticancer potency. Especially, the IC50 of compound 3 is up to 77nm, which was almost matching that of positive control Taxol. Further mechanism study demonstrated that four compounds caused shifts from the soluble tubulin (depolymerized tubulin) to the particulate tubulin fraction (polymerized) which was similar to Taxol.

    9. Design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents

      Subhash Chander, Penta Ashok, Davie Cappoen, Paul Cos and Sankaranarayanan Murugesan

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12788

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      Seventeen, novel quinoline-based carboxylic hydrazides (6a–q) were designed, synthesized, and evaluated for anti-Mtb and cytotoxicity properties, in which compounds 6h, 6j, 6l, and 6m exhibited significant anti-Mtb activity (MIC < 20 μg/mL). None of the compound exhibited cytotoxicity against lung fibroblast cells at tested concentration (512 μm). Structure–activity relationship study of the tested compounds revealed that electron withdrawing group of moderate to large size especially at para position of phenyl ring significantly increased the potency against anti-Mtb while retaining a good safety index.

    10. Design of peptides as inhibitors of human papillomavirus 16 transcriptional regulator E1–E2

      Worrapon Kantang, Surasak Chunsrivirot, Nongnuj Muangsin, Yong Poovorawan and Kuakarun Krusong

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12790

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      Computational approach was used to predict the binding conformations and interactions between the peptides and HPV16 E2. Newly designed Y6R, W4H_Y6R, and W4H peptides more effectively inhibited E1–E2 complex formation than the template peptide.

    11. Metronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase: design, synthesis, and biological evaluation

      Long-Wang Chen, Peng-Fei Wang, Dan-Jie Tang, Xiang-Xiang Tao, Ruo-Jun Man, Han-Yue Qiu, Zhong-Chang Wang, Chen Xu and Hai-Liang Zhu

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12793

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      A series of metronidazole-pyrazole derivatives were designed and synthesized as antibacterial agent to target the tyrosyl-tRNA synthetase (TyrRS). All of the synthesized compounds were examined by bioactivity assays, and the structure–activity relationship was also discussed. Membrane-mediated apoptosis in Pseudomonas aeruginosa induced by compound 4f was verified by flow cytometry.

    12. Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors

      Davide Garella, Sandra Atlante, Emily Borretto, Mattia Cocco, Marta Giorgis, Annalisa Costale, Livio Stevanato, Gianluca Miglio, Chiara Cencioni, Eli Fernández-de Gortari, José L. Medina-Franco, Francesco Spallotta, Carlo Gaetano and Massimo Bertinaria

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12794

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      A series of N-benzoyl amino acid derivatives was synthesized by modulation of three different molecular moieties (A, B, and C). The ability of synthesized compounds to inhibit DNMT-dependent total DNA methylation was evaluated. The most active compound 22 inhibited both DNMT1- and DNMT3A-mediated DNA methylation in a concentration-dependent manner at micromolar concentration. Docking studies suggest putative binding at the substrate site of both DNMT isoforms studied.

    13. Functional reversal of (−)-Stepholidine analogues by replacement of benzazepine substructure using the ring-expansion strategy

      Wei Li, Li Zhang, Lili Xu, Congmin Yuan, Peng Du, Jiaojiao Chen, Xuechu Zhen and Wei Fu

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12796

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      A series of novel ring-expanded analogues of (−)-Stepholidine (l-SPD) were designed, synthesized and bioassayed as potent ligands at D1R. Compound-()-15e (Ki = 5.32 ± 0.01 nm) is more potent than l-SPD (Ki = 13 nm) and was identified as a selective D1R antagonist (IC50 = 0.14 μm). This structural modification was associated with significant increase in selectivity and functional reversal at D1R in comparison with (−)-l-SPD with dual D1R agonistic and D2R antagonistic activities.

    14. PXD101 analogs with L-phenylglycine-containing branched cap as histone deacetylase inhibitors

      Jingyao Li, Xiaoyang Li, Xue Wang, Jinning Hou, Jie Zang, Shuai Gao, Wenfang Xu and Yingjie Zhang

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12787

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      A series of histone deacetylase inhibitors with L-phenylglycine-containing branched cap were synthesized. Compound 10s showed potent HDAC inhibitory activity and moderate in vitro antiproliferative activity..

    15. Angiotensin II analogues with N-terminal lactam bridge cyclization: an overview on AT1 receptor activation and tachyphylaxis

      Flávio Lopes Alves, Vani Xavier Oliveira Jr and Antonio Miranda

      Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12795

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      Angiotensin II is the final active product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. Cyclization in the N-terminal portion of the Angiotensin II with an i-(i+1) lactam bridge consisting an Asp-(Xaa)n-Lys scaffold maintains the contractile activity and do not interfere in the tachyphylaxis phenomenon.

    16. Design, synthesis, and biological evaluation of novel 5-Alkyl-6-Adamantylmethylpyrimidin-4(3H)-ones as HIV-1 non-nucleoside reverse-transcriptase inhibitors

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

      Version of Record online: 21 JUN 2016 | DOI: 10.1111/cbdd.12765

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      A series of novel 5-alkyl-6-adamantylmethylpyrimidin-4(3H)-ones bearing various substituents at the C-2 position of the pyrimidinone ring were synthesized using a facile route and evaluated for their anti-HIV activity in MT-4 cells. The preliminary structure-activity relationship (SAR) and the molecular modeling analysis of these new derivatives are discussed. (SAR) and the molecular modeling analysis of these new derivatives are discussed.

    17. Synthesis and biological evaluation of novel lignan glycosides as anticancer agents

      Ying Wang, Chao Xia, Wei Zhang and Yu Zhao

      Version of Record online: 8 JUN 2016 | DOI: 10.1111/cbdd.12785

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      Eight lignan glycosides were synthesized. Compound 1e displayed strong cytotoxicity and V-ATPase inhibitory activity.

    18. 2-Prenylated m-dimethoxybenzenes as potent inhibitors of 15-lipo-oxygenase: inhibitory mechanism and SAR studies

      Atena Jabbari, Hamid Sadeghian, Alireza Salimi, Mina Mousavian, Seyed M. Seyedi and Mehdi Bakavoli

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12779

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      2,6-dimethoxy-1-isopentenyl-4-methylbenzene, 2,6-dimethoxy-1-geranyl-4-methylbenzene, and 2,6-dimethoxy-1-farnesyl-4-methylbenzene showed the most potent inhibitory activity with IC50 values of 7.6, 5.3, and 0.52 μm, respectively. For some of the compounds, SAR studies showed acceptable relationship between inhibitory potency and enzyme–ligand interactions. Radical scavenging assessment results apart from the SAR studies indicate that electronic properties are the major factors for lipoxygenase inhibition potency of the mentioned compounds.

  6. Research Letters

    1. Water-soluble derivatives of 4-oxo-N-(4-hydroxyphenyl) retinamide: synthesis and biological activity

      Loana Musso, Paola Tiberio, Valentina Appierto, Raffaella Cincinelli, Elena Cavadini, Loredana Cleris, Maria Grazia Daidone and Sabrina Dallavalle

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12781

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      Replacement of the carbonyl group of 4-oxo-4-HPR led to a novel class of water-soluble derivatives that maintained the efficacy and the dual mechanism of action of the parent compound.

  7. Research Articles

    1. Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication

      Ma Min, Jiang Xingjun, Wang Xueding, Zou Hao, Yang Weiqing, Zhang Yuanyuan, Peng Changrong, Li Zicheng, Yang Jing, Du Quan and Ma Menglin

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12774

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      The new arylpropenamide derivatives were synthesized, characterized and evaluated for their anti-HBV activities. A high accuracy 2D and 3D-QSAR models of arylpropenamide were constructed and utilized to predict the activities.

    2. Synthesis of Pyrazine-1,3-thiazine Hybrid Analogues as Antiviral Agent Against HIV-1, Influenza A (H1N1), Enterovirus 71 (EV71), and Coxsackievirus B3 (CVB3)

      Hong-Min Wu, Kuo Zhou, Tao Wu and Yin-Guang Cao

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12769

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      Pyrazine-1,3-thiazine hybrid conjugates were synthesized and subsequently tested against human immunodeficiency virus (HIV-1); hemagglutinin type 1 and neuraminidase type 1—‘Influenza’ A (H1N1) virus; enterovirus 71 (EV71); and coxsackievirus B3.

  8. Research Letters

    1. Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors

      Yeon Sun Lee, Robert Kupp, Michael V. Remesic, Cyf Ramos-Colon, Sara M. Hall, Christopher Chan, David Rankin, Josephine Lai, Frank Porreca and Victor J. Hruby

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12789

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      Various modifications of amphipathic dynorphin A pharmacophore for central bradykinin receptors showed that the position of a Pro residue in analogues is an important feature for the receptor due to the role in making (or disrupting) β-turn or 310helix.

  9. Research Articles

    1. You have full text access to this OnlineOpen article
      Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels–Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors

      Yeray A. Rodríguez, Margarita Gutiérrez, David Ramírez, Jans Alzate-Morales, Cristian C. Bernal, Fausto M. Güiza and Arnold R. Romero Bohórquez

      Version of Record online: 6 JUN 2016 | DOI: 10.1111/cbdd.12773

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      N-allyl/propargyltetrahydroquinolines showed inhibitory activity against cholinesterases. Synthesis of tetrahydroquinolines proceeds via a three-component cationic imino Diels–Alder reaction. The mechanism of enzymatic inhibition was determined by kinetic assays. The computer calculations are consistent with the experimental results.

  10. Review Articles

    1. Allosteric modulators of MEK1: drug design and discovery

      Jialin Shang, Shaoyong Lu, Yongjun Jiang and Jian Zhang

      Version of Record online: 1 JUN 2016 | DOI: 10.1111/cbdd.12780

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      MEK1 allosteric modulators show high anticancer efficacy. We classify four groups of MEK1 modulators by structure. Significant cocrystal structures, current preclinical, and clinical results involving cotherapies are also discussed.

  11. Research Articles

    1. Design, synthesis, and biological characterization of tamibarotene analogs as anticancer agents

      Yuqi Jiang, Xiaoyang Li, Xue Wang, Zhonglan Wang, Jian Zhang, Jingde Wu and Wenfang Xu

      Version of Record online: 1 JUN 2016 | DOI: 10.1111/cbdd.12778

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      HDAC inhibitory activity: IC50 1.8 μm in vivo growth inhibitory activity of HL60 cell: IC50 4.0 μm.

    2. Antibacterial Activity of Imidazolium-Based Ionic Liquids Investigated by QSAR Modeling and Experimental Studies

      Diana Hodyna, Vasyl Kovalishyn, Sergiy Rogalsky, Volodymyr Blagodatnyi, Kirill Petko and Larisa Metelytsia

      Version of Record online: 28 MAY 2016 | DOI: 10.1111/cbdd.12770

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      The developed QSAR models can be used to search for a new active symmetric and asymmetric 1,3-dialkylimidazolium ionic liquids against B. subtilis and Ps. aeruginosa bacterial strains.

    3. Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists

      Chetna Kharbanda, Mohammad Sarwar Alam, Hinna Hamid, Kalim Javed, Sameena Bano, Yakub Ali, Abhijeet Dhulap, Perwez Alam and M. A. Qadar Pasha

      Version of Record online: 27 MAY 2016 | DOI: 10.1111/cbdd.12760

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      Twenty synthesized piperine derivatives are potential antidiabetic agents. Maximum antidiabetic effect was observed for compounds 6c and 6d.

    4. Synthesis and Antiviral Bioassay of New Diphenyl Ether-based Compounds

      Tarek S. Ibrahim, Amany M. M. AL-Mahmoudy, Mohamed Elagawany, Mohamed A. Ibrahim and Siva S. Panda

      Version of Record online: 27 MAY 2016 | DOI: 10.1111/cbdd.12775

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      A series of diphenyl ether-based compounds containing different heterocycles were prepared in good yields and the some of these compounds showed promising in vitro antiviral activity.

    5. Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds

      Ju-feng Sun, Gui-ge Hou, Feng Zhao, Wei Cong, Hong-juan Li, Wen-shuai Liu and Chunhua Wang

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/cbdd.12777

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      Twenty heterocyclic α,β-unsaturated carbonyl compounds are reported. The derivatives were screened against various carcinoma cell lines, which displayed remarkable antiproliferative activity. Meanwhile, their multidrug resistance reversal properties were further examined. In addition, the cellular uptake of HepG2 cells for these compounds was also performed.

    6. Novel Alginate–Chitosan Composite Microspheres for Implant Delivery of Vancomycin and In Vivo Evaluation

      Yimin Mao, Ming Zhao, Yongbiao Ge and Jiang Fan

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/cbdd.12771

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      Vancomycin loaded alginate–chitosan composite microspheres were developed by emulsion cross-linking method. The microspheres were spherical in shape and the mean particle size and drug loading were 25.3 ± 5.4 µm and 18.5 ± 2.3%. In vivo results showed that the application of microspheres not only reduced the toxicity, but also maintained effective drug concentration.

    7. Identification of Damaging nsSNVs in HumanERCC2 Gene

      Shuo Fang, Yuntong Zhang, Miao Xu, Chunyu Xue, Lin He, Lei Cai and Xin Xing

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/cbdd.12772

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      Cutaneous melanoma is a malignant cancer involved with ERCC2 gene. The roles of comprehensive nsSNP in ERCC2 have been studied. Based on the comparison of 3D structure information between the native and mutant proteins, the mutant G713R of ERCC2 protein caused by the rs121913022 is proposed to be the most damaging variant and validated to have less expression level than native ERCC2 in melanoma cells.

    8. Design, Synthesis, and Biological Evaluation of a Novel Water-soluble Prodrug of Docetaxel with Amino Acid as a Linker

      Huan Ma, Gang Chen, Tao Wang, Qingeng Li and Yan Liu

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/cbdd.12762

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      A novel series of derivatives of docetaxel with novel amino acid as a linker were designed, synthesized and evaluated for their antitumor activity. The C2′-modified compound LK-196 behaves as a prodrug; that is, docetaxel is generated upon exposure to human plasma. The compound was also found to have greatly improved water solubility and the self-evident inhibitory effect on tumor growth in vivo, which is a promising candidate for further study.

    9. Influence of S-Oxidation on Cytotoxic Activity of Oxathiole-Fused Chalcones

      Marek T. Konieczny, Anita Buɬakowska, Danuta Pirska, Wojciech Konieczny, Andrzej Skladanowski, Michal Sabisz, Marek Wojciechowski and Krzysztof Lemke

      Version of Record online: 20 MAY 2016 | DOI: 10.1111/cbdd.12776

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      Most of the compounds demonstrated cytotoxic activity at submicromolar concentrations. Oxidation of sulfur atom of the oxathiole-fused chalcones strongly influenced activity of the parent compounds, and depending on relative position of the sulfur atom in the molecule, the activity was either increased or diminished. It was demonstrated that the compounds interact with tubulin at the colchicine binding site.

    10. Boosting Pose Ranking Performance via Rescoring with MM-GBSA

      Paulette A. Greenidge, Richard A. Lewis and Peter Ertl

      Version of Record online: 10 MAY 2016 | DOI: 10.1111/cbdd.12763

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      Self-docking is performed using GOLD ChemPLP. It is shown that rescoring ChemPLP poses with the Molecular Mechanics/Generalized Born Surface Area scoring function improves pose ranking by better discriminating against non-cognate-like poses. In this example, the best pose according to the ChemPLP scoring function has a heavy atom RMSD of 4.7 Å relative to the cognate pose (pink). The MM-GBSA scoring function assigns the best rank to the pose ranked second by GOLD ChemPLP (blue). After the minimization step, the heavy atom RMSD is 0.3 Å relative to the cognate.

    11. An Investigation of the Differential Effects of Ursane Triterpenoids from Centella asiatica, and Their Semisynthetic Analogues, on GABAA Receptors

      Kaiser Hamid, Irene Ng, Vikram J. Tallapragada, Linda Váradi, David E. Hibbs, Jane Hanrahan and Paul W. Groundwater

      Version of Record online: 10 MAY 2016 | DOI: 10.1111/cbdd.12766

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      The ursane triterpenoids, asiatic acid 1 and madecassic acid 2, exhibit selective negative modulation of different subtypes of the GABAA receptor expressed in Xenopus laevis oocytes. Despite differing by only one hydroxyl group, asiatic acid 1 was shown to be a negative modulator of the GABA-induced current at α1β2γ2L (IC50 37.05 μm), followed by α5β3γ2L (IC50 64.05 μm) then α2β2γ2L (IC50 427.2 μm) GABAA receptors, while madecassic acid 2 is not.

    12. Enhanced Loading and Release of Non-Steroidal Anti-Inflammatory Drugs from Silica-Based Nanoparticle Carriers

      Mostafa Mohammadzadeh, Mohammad Sadegh Nourbakhsh, Elham Khodaverdi, Farzin Hadizadeh and Sina Omid Malayeri

      Version of Record online: 9 MAY 2016 | DOI: 10.1111/cbdd.12764

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      Mesoporous silica nanoparticles of SBA-15 have been synthesized and characterized. They were functionalized with aminopropyl, AP@SBA-15. Loading of non-steroidal anti-inflammatory drugs was performed and release profile of these drugs in the simulated gastrointestinal environment were evaluated.

    13. Discovery of 7-Methyl-10-Hydroxyhomocamptothecins with 1,2,3-Triazole Moiety as Potent Topoisomerase I Inhibitors

      Xiguo Xu, Yuelin Wu, Wenfeng Liu, Chuanquan Sheng, Jianzhong Yao, Guoqiang Dong, Kun Fang, Jin Li, Zhiliang Yu, Xiao Min, Huojun Zhang, Zhenyuan Miao and Wannian Zhang

      Version of Record online: 5 MAY 2016 | DOI: 10.1111/cbdd.12767

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      Modifications and SAR of homocamptothecin on position C-10 to the discovery of potent 1,2,3-triazole-substituted derivatives 6j, 6l, and 6o against A549 with IC50 value of 30–50 nm, respectively.

    14. Rational Evolution of Antimicrobial Peptides Containing Unnatural Amino Acids to Combat Burn Wound Infections

      Meng Xiong, Ming Chen and Jue Zhang

      Version of Record online: 5 MAY 2016 | DOI: 10.1111/cbdd.12768

      Thumbnail image of graphical abstract

      A synthetic strategy that integrates quantitative sequence-activity modeling, genetic evolution, dynamics simulation and in vitro assay is described to rationally design antimicrobial peptides containing unnatural amino acids. Four unnatural peptides are successfully identified to have high antibacterial potency, which can fold into amphipathic helical structure.

    15. Quantitative Characterization of the Interaction Space of the Mammalian Carbonic Anhydrase Isoforms I, II, VII, IX, XII, and XIV and their Inhibitors, Using the Proteochemometric Approach

      Behnam Rasti, Mohammad H. Karimi-Jafari and Jahan B. Ghasemi

      Version of Record online: 26 APR 2016 | DOI: 10.1111/cbdd.12759

      Thumbnail image of graphical abstract

      Using the proteochemometric approach (PCM), we could find remarkable information that can be taken into consideration for designing inhibitors with the ability of selective inhibition of either cytosolic isoforms or transmembrane isoforms of carbonic anhydrase.

    16. Conjugation of Uridine with Oleanolic Acid Derivatives as Potential Antitumor Agents

      Ke-Guang Cheng, Chun-Hua Su, Jia-Yan Huang, Jun Liu, Yuan-Ting Zheng and Zhen-Feng Chen

      Version of Record online: 18 APR 2016 | DOI: 10.1111/cbdd.12758

      Thumbnail image of graphical abstract

      Ten targeted uridine–oleanolic acid hybrids were synthesized. Most of these hybrids showed excellent proliferation inhibition against tested Hep-G2, A549, BGC-823, MCF-7, and PC-3 tumor cell lines (IC50 < 8 μm), even with some IC50 values of them under 0.1 μm.

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