Chemical Biology & Drug Design

Cover image for Vol. 88 Issue 3

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

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  1. 1 - 41
  1. Research Articles

    1. Design, synthesis, and in vitro antimicrobial activity of hydrazide–hydrazones of 2-substituted acetic acid

      Łukasz Popiołek and Anna Biernasiuk

      Version of Record online: 27 AUG 2016 | DOI: 10.1111/cbdd.12820

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      Synthesis and in vitro antimicrobial activity of hydrazide-hydrazones of 2-substituted acetic acid.

    2. 3-aminopyrazolopyrazine derivatives as spleen tyrosine kinase inhibitors

      Jiayi Shen, Xiaokai Li, Zhang Zhang, Jingfeng Luo, Huoyou Long, Zhengchao Tu, Xiaoping Zhou, Ke Ding and Xiaoyun Lu

      Version of Record online: 27 AUG 2016 | DOI: 10.1111/cbdd.12798

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      A series of pyrazolopyrazine-3-amine and pyrazolopyrimidine-3-amine derivatives were designed and synthesized as new spleen tyrosine kinase inhibitors. The efforts yielded compound 6h with promising spleen tyrosine kinase inhibition in both enzymatic and B-lymphoma cells proliferation assays.

    3. Synthesis, biological evaluation, and molecular docking studies of new pyrazol-3-one derivatives with aromatase inhibition activities

      Xue-Jing Yi, Tamer T. El-Idreesy, Taha M. A. Eldebss, Ahmad M. Farag, Mohamed M. Abdulla, Shaimaa A. Hassan and Yahia N. Mabkhot

      Version of Record online: 27 AUG 2016 | DOI: 10.1111/cbdd.12812

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      A new series of pyrazol-3-one derivatives was synthesized, characterized and its pharmacological activity towards aromatase enzyme inhibition was screened and compared to the reference native ligand Letrozole. The findings were also supported by molecular docking studies.

    4. Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid

      Riaz A. Khan

      Version of Record online: 20 AUG 2016 | DOI: 10.1111/cbdd.12821

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      Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized in solution-phase with a simultaneous a-amino and carboxyl group's protection of the l-Methionine (l-Met) as PTSA.Met-OBzl towards a C-terminal 2 + 2 + 1 fragments condensation convergent approach. The strategy provided a stable, robust, and feasible procedure to carry through the coupling between Boc-Phe-OH and deprotected PTSA-Met-OBzl to produce one of the designated dipeptide fragments, Boc-Phe-Met-OBzl. Devoid of any structural deformities, and near quantitative yields, the cost-effective, single step, orthogonal protection with process's racemization under control made the strategy suitable for scale-up towards feasible synthesis of the pentapeptide.

    5. A small molecule identified through an in silico screen inhibits Aurora B–INCENP interaction

      Esra Unsal, Bahar Degirmenci, Büşra Harmanda, Burak Erman and Nurhan Ozlu

      Version of Record online: 20 AUG 2016 | DOI: 10.1111/cbdd.12816

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      A structure-based virtual screen was performed to target the interaction between Aurora B kinase and its activator INCENP. In silico molecular docking analysis identified five potential candidates of 200 000 compounds, which selectively bind to the Aurora B::INCENP interaction site but not to the ATP-binding site (kinase pocket) of Aurora B and other fourteen related kinases. Further characterization in vivo validated the inhibitory role of one of these five compounds in Aurora B:INCENP complex formation.

  2. Research Letters

    1. Design and synthesis of 4′-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors

      Firoz A. Kalam Khan, Rajendra H. Patil, Devanand B. Shinde and Jaiprakash N. Sangshetti

      Version of Record online: 17 AUG 2016 | DOI: 10.1111/cbdd.12817

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      Synthesis and evaluation of 4′-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a–j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value = 139.28 μM), 11g (IC50 value = 136.18 μM), and 11h (IC50 value = 131.65 μM) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36–167.26 μg/mL), 11g (MIC range = 93.75–145.67 μg/mL), and 11h (MIC range = 63.61–126.63 μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00–250.00 μg/mL).

  3. Research Articles

    1. Preparation, characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study

      Donya Poy, Azim Akbarzadeh, Hasan Ebrahimi Shahmabadi, Meysam Ebrahimifar, Ali Farhangi, Maryam Farahnak Zarabi, Azam Akbari, Zahra Saffari and Fatemeh Siami

      Version of Record online: 17 AUG 2016 | DOI: 10.1111/cbdd.12786

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      Cisplatin was encapsulated into pegylated liposomal nanoparticles by reverse phase evaporation technique. Nanoparticles were characterized by dynamic light scattering technique, atomic force microscopy (AFM), spectrophotometry, Fourier transform infrared spectroscopy, and MTT assay. Proper drug-loading efficiency and drug retention capability, along with augment cytotoxicity effects, were observed. In addition, the results of AFM microscopy confirmed the nanoparticles formation.

    2. Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

      Jing Leng, Hua-Li Qin, Kaicheng Zhu, Ibrahim Jantan, Muhammad Ajaz Hussain, Muhammad Sher, Muhammad Wahab Amjad, Muhammad Naeem-ul-Hassan, Waqas Ahmad and Syed Nasir Abbas Bukhari

      Version of Record online: 17 AUG 2016 | DOI: 10.1111/cbdd.12822

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      Effects of a series of α, β-unsaturated carbonylbased tetralone derivatives against Alzheimer's disease (AD) were investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO-B, AChE and self-induced Aβ1–42 aggregation. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.

    3. Docetaxel–Chitosan nanoparticles for breast cancer treatment: cell viability and gene expression study

      Zahra H. Mirzaie, Shiva Irani, Reza Mirfakhraie, Seyed Mohammad Atyabi, Meshkat Dinarvand, Rassoul Dinarvand, Reyhaneh Varshochian and Fatemeh Atyabi

      Version of Record online: 17 AUG 2016 | DOI: 10.1111/cbdd.12814

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      Less toxic effect of DTX-conjugated nanoparticles on normal cells was observed in comparison with cancerous cells. The ratio of BAX/BCL2 was optimized to conduct the fate of cell toward apoptosis. Suitable uptake of DTX-conjugated nanoparticles to the cell was also observed.

    4. Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer

      Aastha Singh, Kaneez Fatima, Ankita Srivastava, Sadiya Khwaja, Dev Priya, Arjun Singh, Girish Mahajan, Sarfaraz Alam, Ajit K. Saxena, D. M. Mondhe, Suaib Luqman, Debabrata Chanda, Feroz Khan and Arvind S. Negi

      Version of Record online: 6 AUG 2016 | DOI: 10.1111/cbdd.12805

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      2-Benzylidene indanones have been synthesized. The detailed pharmacology of the best analogue (Compound 8) of the series has been explored.

    5. Synthesis, structure–activity relationship studies and biological evaluation of novel 2,5-disubstituted indole derivatives as anticancer agents

      Hongyu Hu, Jun Wu, Mingtao Ao, Huiru Wang, Tongtong Zhou, Yuhua Xue, Yingkun Qiu, Meijuan Fang and Zhen Wu

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/cbdd.12808

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      Three novel series of 2,5-disubstituted indole derivatives were synthesized. Among them, 2c and 3b which had a pan anti-proliferative activity against human cancer cells and showed effectively HIV-1 inhibition activity, may induce cancer cells apoptosis through inhibiting the phosphorylation at Ser2 of RNAPII CTD which can be phosphorylated by cyclin-dependent kinase 9.

    6. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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. 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.

  8. 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.

    2. 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. 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.

    3. 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.

    4. 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.

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