Chemical Biology & Drug Design

Cover image for Vol. 89 Issue 1

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); 138/289 (Biochemistry & Molecular Biology)

Online ISSN: 1747-0285


  1. 1 - 56

    1. Structure–function relationship of Chikungunya nsP2 protease: A comparative study with papain

      Chandrasekaran Ramakrishnan, Nidamarthi H. V. Kutumbarao, Sivasubramanian Suhitha and Devadasan Velmurugan

      Version of Record online: 5 JAN 2017 | DOI: 10.1111/cbdd.12901

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      Structure–function relationship of Chikungunya virus-nsP2 and papain proteases is studied. Based on the active site similarity, the papain inhibitors were analyzed using in silico studies for their efficacy in binding Chikungunya virus-nsP2. Based on molecular docking and MD simulation results, we report that four papain inhibitors can be good lead compounds for Chikungunya virus-nsP2 protease inhibition.


    1. Breast tumor stroma: A driving force in the development of resistance to therapies

      Maryam Majidinia and Bahman Yousefi

      Version of Record online: 2 JAN 2017 | DOI: 10.1111/cbdd.12893

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      Tumor stroma is a key player in cancer progression and response to therapy. Breast tumor–stromal interaction is a driving force in multidrug-resistant development. A better understanding of the clinically active breast tumor–stromal interactions might help to developing effective therapeutic strategies for patients with drug-resistant status.


    1. CCND1-BCL2 Gene Network: A direct target of Amifostine in human acute megakaryocytic leukemia cells

      Feng Zhang, Bo Yang, Kailiang Zhang, Mei-Ling Hou, Xue-chun Lu and Yu-Xin Li

      Version of Record online: 2 JAN 2017 | DOI: 10.1111/cbdd.12889

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      In order to examine the effects and mechanisms underlying the effects of amifostine on human acute megakaryocytic leukemia, we evaluated the efficacy of amifostine against Dami cells and observed a cell cycle arrest in G2/M phase. Amifostine treatment also induced cell apoptosis of Dami cell which corresponds to formal studies. Through whole-genome microarray and bioinformatics analyses, we found that amifostine affected the gene expression of CCND1, BCL2, CASP3 which revealed the mechanism amifostine acted on Dami cells. Thus, CCND1-BCL2 Gene Network is predicted to be a direct target of amifostine treating human acute magakaryocytic leukemia.

    2. Synthesis and biological evaluation of novel imidazopyrimidin-3-amines as anticancer agents

      Mohammad Mahdavi, Shima Dianat, Behnaz Khavari, Setareh Moghimi, Mohammad Abdollahi, Maliheh Safavi, Arash Mouradzadegun, Sussan Kabudanian Ardestani, Reyhaneh Sabourian, Saeed Emami, Tahmineh Akbarzadeh, Abbas Shafiee and Alireza Foroumadi

      Version of Record online: 29 DEC 2016 | DOI: 10.1111/cbdd.12904

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      A series of imidazo[1,2-a]pyrimidines 6a–o were synthesized as novel anticancer agents. Some of them were more potent than etoposide. Particularly, compound 6c was fivefold more potent than etoposide against T-47D cells (IC50 = 6.72 μm).

  4. Research Articles

    1. You have full text access to this OnlineOpen article
      Gemcitabine-(5′-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549)

      Cody P. Coyne and Lakshmi Narayanan

      Version of Record online: 20 DEC 2016 | DOI: 10.1111/cbdd.12845

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      A multistage organic chemistry reaction strategy was utilized to synthesize gemcitabine-(5′-phosphoramidate)-[anti-IGF-1R] that possesses properties of selective ‘targeted’ delivery and antineoplastic cytotoxic potency. The flexible non-dedicated synthesis method is rapid and efficient with minimal or no side reactions. Attributes of gemcitabine-(5′-phosphoramidate)-[anti-IGF-1R] include a high gemcitabine molar incorporation index, ability to effectively evoke cytotoxic antineoplastic activity, potential to provide a wide margin of safety, and an ability to evoke greater levels of selective ‘targeted’ antineoplastic cytotoxicity in vivo through activation of antibody-dependent cell cytotoxicity, complement pathways, and opsonization.

    2. ENRI: A tool for selecting structure-based virtual screening target conformations

      Rahmad Akbar, Siti Azma Jusoh, Rommie E. Amaro and Volkhard Helms

      Version of Record online: 20 DEC 2016 | DOI: 10.1111/cbdd.12900

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      Selecting optimal SBVS targets remains a challenging undertaking. We present here a method to extract optimal targets for SBVS experiments. Among seven nuclear receptors, the method was able to identify high-enrichment targets in six of seven nuclear receptors. The best performing target identified by our method yielded a twofold enrichment over the corresponding experimentally determined conformation.

    3. Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro

      Sourav Kumar, Ashim Paul, Sourav Kalita, Anup Kumar Ghosh, Bhubaneswar Mandal and Amal Chandra Mondal

      Version of Record online: 20 DEC 2016 | DOI: 10.1111/cbdd.12912

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      This study demonstrated that BSBHp could effectively ameliorate Aβ40-induced oxidative stress and apoptosis in human neuroblastoma SF-SY5Y cell in vitro by inhibiting Aβ40 aggregation. This is the first report to demonstrate that BSBHp has the neuroprotective effects against Aβ-induced neurotoxicity in SH-SY5Y cells. The protection effects of BSBHp against neuronal atrophy may help to provide the pharmacological basis for the treatment of Alzheimer's disease.

    4. Synthesis and anticholinesterase activity of new substituted benzo[d]oxazole-based derivatives

      Behjat Pouramiri, Setareh Moghimi, Mohammad Mahdavi, Hamid Nadri, Alireza Moradi, Esmat Tavakolinejad-Kermani, Loghman Firoozpour, Ali Asadipour and Alireza Foroumadi

      Version of Record online: 11 DEC 2016 | DOI: 10.1111/cbdd.12902

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      A series of novel benzo[d]oxazole-based derivatives were synthesized as novel anticholinesterase agents. The inhibitory activities against AChE and BChE were more potent than donepezil. 2-(4-((Piperidin-1-yl)methyl)phenyl)benzo[d]oxazole exhibited dual inhibitory activity against BChE (two times stronger than reference drug) and moderate activity against AChE.

  5. Review Articles

    1. Structural and biochemical insights into the allosteric activation mechanism of AMP-activated protein kinase

      Jin Li, Shuying Li, Fengzhong Wang and Fengjiao Xin

      Version of Record online: 9 DEC 2016 | DOI: 10.1111/cbdd.12897

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      AMP-activated protein kinase (AMPK) is widely studied as a potential drug target for treatment of type 2 diabetes (T2D), cancers, and cardiovascular diseases. Its phosphorylation in α-Thr172 by upstream kinases is crucial for basal activity and AMP, and its analogues binding to γ subunit causes further allosteric activation. The review summarizes the domain constitutions of mammalian AMPK and then systematically describes its allosteric activation mechanism from a structural and biochemical view.

  6. Research Articles

    1. Identification and structure–activity relationship of purine derivatives as novel MTH1 inhibitors

      Ashutosh Kumar, Tatsuro Kawamura, Makoto Kawatani, Hiroyuki Osada and Kam Y. J. Zhang

      Version of Record online: 7 DEC 2016 | DOI: 10.1111/cbdd.12909

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      A series of compounds belonging to the purine scaffold have been screened for MTH1 inhibitory activity, and several new inhibitors with potency in the submicromolar range have been discovered. The structure activity relationship of these compounds has been analyzed, and their associated binding modes to MTH1 have been predicted using molecular docking. These studies have provided insights for the development of highly potent MTH1 inhibitors.

    2. Theoretical studies on the selective mechanisms of GSK3β and CDK2 by molecular dynamics simulations and free energy calculations

      Sufang Zhao, Jingyu Zhu, Lei Xu and Jian Jin

      Version of Record online: 7 DEC 2016 | DOI: 10.1111/cbdd.12907

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      A computational strategy, which combines molecular docking, molecular dynamics simulations, free energy calculations and umbrella sampling simulations, was employed to explore the binding mechanisms of two selective inhibitors to GSK3β and CDK2. The inhibitor specificity between GSK3β and CDK2 is determined by the additive contributions of multiple amino acids.

    3. Downregulation of MicroRNA-320d predicts poor overall survival and promotes the growth and invasive abilities in glioma

      Chong-Zhen Qin, Qiao-Li Lv, Yan-Tao Yang, Jing-Min Zhang, Xiao-Jian Zhang and Hong-Hao Zhou

      Version of Record online: 5 DEC 2016 | DOI: 10.1111/cbdd.12906

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      This study is the first to demonstrate that miR-320d expression was significantly decreased in glioma tissues and cell lines. Mechanism analysis showed that overexpression of miR-320d could significantly suppress cell growth, migration and invasion, and induced cell apoptosis, cell cycle at G0/G1 arrest, as well as invasion-related molecules in U87 and U251 cell lines, indicating that miR-320d may serve as a prognostic and therapy biomarker in glioma.

    4. Graph theoretical analysis, insilico modeling, design, and synthesis of compounds containing benzimidazole skeleton as antidepressant agents

      Panneerselvam Theivendren, Arumugam Subramanian, Indhumathy Murugan, Shrinivas D. Joshi and Uttam A. More

      Version of Record online: 2 DEC 2016 | DOI: 10.1111/cbdd.12894

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      The 4-(1H-benzo[d]imidazol-2-yl)-N-(substituted phenyl)-4-oxobutanamide (3a–j) have been synthesized to meet the structural requirements essential for antidepressant activity.

    5. Design, synthesis, and biological evaluation of pyrimidine derivatives as potential inhibitors of human calcium/calmodulin-dependent protein kinase IV

      Ehtesham Jameel, Huma Naz, Parvez Khan, Mohd. Tarique, Jitendra Kumar, Syed Mumtazuddin, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Nasimul Hoda and Md. Imtaiyaz Hassan

      Version of Record online: 2 DEC 2016 | DOI: 10.1111/cbdd.12898

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      Seven molecules were successfully synthesized having pyrimidine scaffolds. Compound 1 is showing best binding affinity to calcium/calmodulin-dependent protein kinase IV. Compound 1 has best IC50 value, and anticancer properties.

    6. Synthesis and preliminary evaluation of a 99mTc-labeled folate-PAMAM dendrimer for FR imaging

      Manli Song, Zhide Guo, Mengna Gao, Changrong Shi, Duo Xu, Linyi You, Xiaowei Wu, Xinhui Su, Rongqiang Zhuang, Weimin Pan, Ting Liu and Xianzhong Zhang

      Version of Record online: 2 DEC 2016 | DOI: 10.1111/cbdd.12899

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      A FA-conjugated PAMAM dendrimer was synthesized and radiolabeled with 99mTc successfully. Our results show that this folate-PAMAM dendrimer has the potential as a non-invasive radioactive diagnostic imaging agent for the detection of FR-positive cancers. Furthermore, this versatile strategy can be extended to sensitive multimodal imaging and/or enhanced therapy of different cancers.

    7. New insights into the structure of the trace amine-associated receptor 2: Homology modelling studies exploring the binding mode of 3-iodothyronamine

      Elena Cichero and Michele Tonelli

      Version of Record online: 29 NOV 2016 | DOI: 10.1111/cbdd.12903

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      mTAAR2 and hTAAR2 homology models have been built for the first time. At present, only 3-iodothyronamine (T1AM) acts as TAAR2 ligand, being also able to bind other TAARs, making the discovery of selective compounds an urgent need to derive efficient tools for studying this family of receptors. The two models have been compared with those we previously built about the mTAAR1 and hTAAR1 receptors. New insights guiding for species specificity and selectivity between the TAAR1 and TAAR2 receptors have been derived.

    8. 1H-1,2,3-triazole-tethered uracil-ferrocene and uracil-ferrocenylchalcone conjugates: Synthesis and antitubercular evaluation

      Amandeep Singh, Christophe Biot, Albertus Viljoen, Christian Dupont, Laurent Kremer, Kewal Kumar and Vipan Kumar

      Version of Record online: 29 NOV 2016 | DOI: 10.1111/cbdd.12908

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      Synthesis and antitubercular evaluation of 1H-1,2,3-triazole-tethered uracil-ferrocene and uracil-ferrocenylchalcone conjugates.

    9. Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces mitotic arrest

      Fangjin Chen, Xiaolong Zhuo, Tan Qin, Xiao Guo, Chuanmao Zhang and Luhua Lai

      Version of Record online: 24 NOV 2016 | DOI: 10.1111/cbdd.12896

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      Inhibitor target the nuclear localization signal (NLS) of polo-like kinase 1 (Plk1) was rationally designed through virtual screening. The NLS inhibitor D110 strongly inhibits the activity of Plk1 with the IC50 of 85 nm. D110 inhibits the translocation of Plk1 into nucleus in HeLa cells during interphase.

    10. Microsecond molecular dynamics simulations provide insight into the ATP-competitive inhibitor-induced allosteric protection of Akt kinase phosphorylation

      Linkai Mou, Tongwei Cui, Weiguang Liu, Hong Zhang, Zhanxiu Cai, Shaoyong Lu and Guojun Gao

      Version of Record online: 24 NOV 2016 | DOI: 10.1111/cbdd.12895

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      Molecular dynamics simulations were performed to illustrate the molecular mechanism for allosteric regulation of Akt1 kinase phosphorylation by binding of ATP-competitive inhibitor GDC-0068 to the ATP-binding site. We propose a potential mechanism and identify a communication pathway from GDC-0068 to pT308 in Akt1. This result yields important new insights into the molecular mechanism of allosteric regulation of Akt kinase activity.

    11. 5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives with in vitro immunomodulatory activities

      Angelika Drynda, Bożena Obmińska-Mrukowicz, Ewa Zaczyńska, Michał Zimecki, Iwona Kochanowska, Stanisław Ryng and Marcin Mączyński

      Version of Record online: 24 NOV 2016 | DOI: 10.1111/cbdd.12892

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      Two of the most active isoxazole derivatives were chosen from the obtained series of 5-amino-3-methyl-4-isoxazolecarboxylic acid semicarbazides and thiosemicarbazides. Immunomodulatory activity in primary cell cultures of ‘old’ and ‘young’ mice and possible mechanism of action is reported. 06K derivative showed different, immunosuppressive characteristics than the parent compound, while 01K compound exhibited promising regulatory activity in cells isolated from ‘old’ mice.

  7. Research Letters

    1. Synthesis of new arylisoxazole–oxindole conjugates as potent antiproliferative agents

      Gajjela Bharath Kumar, Syed Nasir Abbas Bukhari and Hua-Li Qin

      Version of Record online: 19 NOV 2016 | DOI: 10.1111/cbdd.12884

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      Development of an efficient and versatile convergent synthetic procedure for the preparation of a new series of arylisoxazole–oxindole conjugates. Compounds with methoxy substituent on D ring exhibited better cytotoxic effect against all the cell lines than the compounds bearing nitro substituent in the same ring.

  8. Research Articles

    1. Validation of flavonoids as potential dipeptidyl peptidase III inhibitors: Experimental and computational approach

      Dejan Agić, Hrvoje Brkić, Sanja Tomić, Zrinka Karačić, Marija Špoljarević, Miroslav Lisjak, Drago Bešlo and Marija Abramić

      Version of Record online: 19 NOV 2016 | DOI: 10.1111/cbdd.12887

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      Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III; 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity while molecular dynamics results clearly provide valuable information explaining the importance of flavonoid hydroxyl groups in the mechanism for the binding pattern at the active site of hDPP III.

    2. Synthesis and evaluation of novel amonafide–polyamine conjugates as anticancer agents

      Yuxia Wang, Jianying Zhang, Meng Li, Ming Li, Songqiang Xie and Chaojie Wang

      Version of Record online: 19 NOV 2016 | DOI: 10.1111/cbdd.12888

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      The in vitro trials revealed that the presence of aspirin elevated the potency of 6k against tumor cells. The in vivo trials on three H22 tumor transplant models demonstrated that the combination of 6k and aspirin markedly improved the efficacy in terms of inhibitive effect, pulmonary metastasis, and extension of the life span. More importantly, the combination of 6k and aspirin displayed the reduced side effects compared to that of amonafide.

    3. Positive cooperative regulation of double binding sites for human acetylcholinesterase

      Hao Liu, Wei Ye and Hai-Feng Chen

      Version of Record online: 19 NOV 2016 | DOI: 10.1111/cbdd.12891

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      Dynamics correlation network of hAChE/TZ5 includes hub nodes.

  9. Research Letter

    1. Synthesis and biological evaluation of 1, 2, 4-oxadiazole derivatives as novel GPR119 agonists

      Suhong Fu, Wei Xiang, Jinying Chen, Liang Ma and Lijuan Chen

      Version of Record online: 19 NOV 2016 | DOI: 10.1111/cbdd.12890

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      Twenty-five 1, 2, 4-oxadiazol derivatives were evaluated their abilities in GPR119-transfected HEK293T cells by the assay of cAMP concentration. SAR study indicated that six-membered ring containing two nitrogen atoms was favorable for potency. All compounds showed acceptable agonistic effects on GPR119. Among these compounds, compound 4p showed highly potent agonistic activity (EC50 = 20.6 nm).

  10. Research Articles

    1. Computed insight into a peptide inhibitor preventing the induced fit mechanism of MurA enzyme from Pseudomonas aeruginosa

      Anderson H. Lima, Alberto M. dos Santos, Cláudio Nahum Alves and Jerônimo Lameira

      Version of Record online: 16 NOV 2016 | DOI: 10.1111/cbdd.12882

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      In this article, theoretical simulations were used to analyze, for the first time, the interaction of the PEP 1354 peptide with MurA enzyme from Pseudomonas aeruginosa. Our modeling results suggest that the peptide binds to the same active site of the natural substrate UDP-N-acetylglucosamine. Additionally, the MurA–peptide complex reveals that the peptide seems to act preventing the closure of the loop Pro114-123 and consequently, the open–closed transition of MurA structure.

    2. The small-molecule 3G11 inhibits HIV-1 reverse transcription

      Silvana Opp, Thomas Fricke, Caitlin Shepard, Dmytro Kovalskyy, Akash Bhattacharya, Frank Herkules, Dmitri N. Ivanov, Baek Kim, Jose Valle-Casuso and Felipe Diaz-Griffero

      Version of Record online: 15 NOV 2016 | DOI: 10.1111/cbdd.12886

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      3G11 binds to capsid and blocks HIV-1 reverse transcription during infection.

    3. Structure–activity relationship of caffeic acid phenethyl ester analogs as new 5-lipoxygenase inhibitors

      Jérémie A. Doiron, Luc M. Leblanc, Martin J. G. Hébert, Natalie A. Levesque, Aurélie F. Paré, Jacques Jean-François, Marc Cormier, Marc E. Surette and Mohamed Touaibia

      Version of Record online: 15 NOV 2016 | DOI: 10.1111/cbdd.12874

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      A series of caffeic acid phenethyl ester (CAPE) analogs was synthesized and screened in vitro for their ability to inhibit 5-lipoxygenase (5-LO) along with 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay. Many screened compounds outperformed CAPE in concentration-dependent assays on HEK293 cell models and human polymorphonuclear leukocytes, caffeoyl ethers 7a–b being roughly sevenfold and 16-fold more potent than Zileuton, the only 5-LO inhibitor currently approved for human therapy.

    4. Anionic chlorido(triphenyl)tin(IV) bearing N-phthaloylglycinato or 1,2,4-benzenetricarboxylato 1,2-anhydride ligands: potential cytotoxic and apoptosis-inducing agents against several types of cancer

      Denise Hübner, Milena R. Kaluđerović, Santiago Gómez-Ruiz and Goran N. Kaluđerović

      Version of Record online: 15 NOV 2016 | DOI: 10.1111/cbdd.12885

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      Two ionic triphenyltin(IV) chloride carboxylate compounds (N-phthaloylglycine, 1; 1,2,4-benzenetricarboxylate 1,2-anhydride ligand, 2) were tested for the in vitro activity against 518A2 (melanoma), FaDu (head and neck carcinoma), HT-29 (colon cancer), MCF-7 (breast carcinoma), and SW1736 (thyroid cancer) cell lines. Both organotin(IV) compounds showed potent cytotoxic and apoptotic properties against tested cancer cell lines.

    5. Synthesis and preliminary evaluation of a 18F-labeled ethisterone derivative [18F]EAEF for progesterone receptor targeting

      Xiaowei Wu, Linyi You, Deliang Zhang, Mengna Gao, Zijing Li, Duo Xu, Pu Zhang, Lumei Huang, Rongqiang Zhuang, Hua Wu and Xianzhong Zhang

      Version of Record online: 15 NOV 2016 | DOI: 10.1111/cbdd.12878

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      A novel ethisterone derivative-based probe [18F]EAEF was developed for positron emission tomography imaging of progesterone receptor. High uptakes in PR-positive tissues (breast tumor, uterus, and ovary) and good target-to-background ratios were observed in tumor bearing mice, indicating that [18F]EAEF might be a promising candidate for PR-positive breast cancer diagnosis with positron emission tomography imaging.

    6. Preparation, characterization, and in vitro evaluation of bleomycin-containing nanoliposomes

      Mohsen Chiani, Mohammad Ali Shokrgozar, Kayhan Azadmanesh, Dariush Norouzian, Mohammad Reza Mehrabi, Aazam Najmafshar and Azim Akbarzadeh

      Version of Record online: 10 NOV 2016 | DOI: 10.1111/cbdd.12869

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      Bleomycin-containing nanoliposomes were successfully prepared and characterized. PEG-nLip-BLM showed excellent stability, high loading efficacy, and improved cytotoxicity against LLC1 cells and good retention capability compare to nLip-BLM and free drug. These findings will facilitate the production of a new formulation of BLM with long-acting action and more efficient anticancer activity for testing on human subjects.

    7. Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives as potential antitumor candidate

      Panhu Zhu, Wenfeng Ye, Jiaming Li, Yanchun Zhang, Weijun Huang, Mohan Cheng, Yujun Wang, Yang Zhang, Huicai Liu and Jian Zuo

      Version of Record online: 10 NOV 2016 | DOI: 10.1111/cbdd.12873

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      A novel class of tetrahydroisoquinoline derivatives was designed and synthesized. The antiproliferative activities of all the target compounds on HUVEC, MCF-7, and HT-29 were evaluated, and 17d and 17e exhibited outstanding activity on MCF-7. Our research confirmed that 17d and 17e were better inhibitor of tubulin polymerization. In addition, compounds 17d and 17e demonstrated potent in vivo efficacy. In summary, these findings suggest that 17d and 17e are promising novel agents for the potential treatment of cancer.

    8. Clarifying binding difference of ATP and ADP to extracellular signal-regulated kinase 2 by using molecular dynamics simulations

      Jianzhong Chen

      Version of Record online: 10 NOV 2016 | DOI: 10.1111/cbdd.12877

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      Insight into the binding difference of ADP and ATP to extracellular signal-regulated kinase 2 (ERK2) is significant for designs of potent inhibitors targeting ERK2.

  11. Research Letter

    1. Identification of ginkgolide targets in brain by photoaffinity labeling

      Akira Kawamura, Ilyas Washington, Doina M. Mihai, Francesca Bartolini, Gregg G. Gundersen, Milica Tesic Mark and Koji Nakanishi

      Version of Record online: 10 NOV 2016 | DOI: 10.1111/cbdd.12883

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      Photoactive analogs of ginkgolide selectively photolabeled α-tubulin in bovine hippocampus homogenate. Furthermore, ginkgolides exhibited unique effects on tubulin biology, including inhibition of microtubule detyrosination. The finding heralds a new chapter of the research on ginkgolides whose biological potential is yet to be discovered.

  12. Research Articles

    1. Discovery of selective protein arginine methyltransferase 5 inhibitors and biological evaluations

      Sen Ji, Shuang Ma, Wen-Jing Wang, Shen-Zhen Huang, Tian-qi Wang, Rong Xiang, Yi-Guo Hu, Qiang Chen, Lin-Li Li and Sheng-Yong Yang

      Version of Record online: 10 NOV 2016 | DOI: 10.1111/cbdd.12881

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      In this investigation, we discovered new potent PRMT5 inhibitors with the aid of computer-aided virtual screening and structure–activity relationship analysis. P5i-6 could be used as a chemical probe to investigate new functions of PRMT5 in biology and also served as a good lead compound for the development of new PRMT5-targeting therapeutic agents.

    2. 99mTc-anti-epidermal growth factor receptor nanobody for tumor imaging

      Majid Piramoon, Seyed Jalal Hosseinimehr, Kobra Omidfar, Zohreh Noaparast and Seyed Mohammad Abedi

      Version of Record online: 5 NOV 2016 | DOI: 10.1111/cbdd.12871

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      This study described the preparation and radiolabeling of anti-EGFR nanobody, OA-cb6. The nanobody was labeled using 99mTc-tricarbonyl. Results showed that radioconjugate had fast blood clearance and a favorable tumor uptake in A431-xenografted nude mice.

    3. Synthesis and evaluation of anti-inflammatory properties of silver nanoparticle suspensions in experimental colitis in mice

      Krzysztof Siczek, Hubert Zatorski, Anna Chmielowiec-Korzeniowska, Jolanta Pulit-Prociak, Magdalena Śmiech, Radzisław Kordek, Leszek Tymczyna, Marcin Banach and Jakub Fichna

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12876

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      Two silver nanoparticle aqueous solutions NanoAg1 and NanoAg2 varying in size and shape were developed by one-step chemical reduction with the involvement of tannic acid. NanoAg1 and NanoAg2 significantly ameliorated colitis in mouse models of colonic inflammation mimicking human ulcerative colitis and Crohn's disease. The anti-inflammatory effect was dependent on the shape and diameter of silver nanoparticles. Our study shows that NanoAg1 and NanoAg2 have the potential to become valuable agents for the treatment of IBD.

    4. In silico prediction and in vitro and in vivo validation of acaricide fluazuron as a potential inhibitor of FGFR3 and a candidate anticancer drug for bladder carcinoma

      Kunbin Ke, Hongjian Li, Hong Yao, Xi-Nan Shi, Chao Dong, Ying Zhu, Xu Liu, Ling Li, Kwong-Sak Leung, Man-Hon Wong, Xiao-Dong Liu, Hsiang-fu Kung and Marie Chia-mi Lin

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12872

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      We utilized the free and open-source protein–ligand docking software idock to prospectively identify potential inhibitors of FGFR3. The fluazuron exhibited the highest anticancer effect in human bladder carcinoma cell lines, RT112 and RT4, and inhibited the FGFR3 signaling pathway in vitro. Oral treatment with fluazuron significantly inhibited tumor growth in BALB/C nude mice. These results suggested for the first time that fluazuron is a potential inhibitor of FGFR3 and a candidate anticancer drug for the treatment of bladder cancer.

    5. Synthesis of honokiol analogues and evaluation of their modulating action on VEGF protein secretion and telomerase-related gene expressions

      María Sánchez-Peris, Juan Murga, Eva Falomir, Miguel Carda and Juan Alberto Marco

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12880

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      A group of 36 biphenyl derivatives structurally related to honokiol were synthesized by means of Suzuki coupling reactions. Their cytotoxicities were evaluated and compared to that of honokiol. Some of the compounds were then evaluated for their ability to downregulate the secretion of the VEGF protein and the expression of the VEGF, hTERT, and c-Myc genes; the two latter involved in the activation of telomerase in tumoral cells.

    6. Synthesis and cytotoxic activity of certain benzothiazole derivatives against human MCF-7 cancer cell line

      Lamia W. Mohamed, Azza T. Taher, Ghada S. Rady, Mamdouh M. Ali and Abeer E. Mahmoud

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12879

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      A new series of benzothiazole has been synthesized as cytotoxic agents. The new derivatives were tested for their cytotoxic activity toward the human breast cancer MCF-7 cell line against cisplatin as the reference drug. Many derivatives revealed good cytotoxic effect, whereas four of them, 4, 5c, 5d, and 6b, were more potent than cisplatin, with IC50 values being 8.64, 7.39, 7.56, and 5.15 µm compared to 13.33 µm of cisplatin.

    7. In vitro evaluation of apoptotic effect of bis(acetylacetonato-k2 O,O′)(1,10-phenanthroline-k2 N,N′)Zn(II) complex

      Cristina Trejo-Solis, Mayra A. Alvarez-Lemus, Dolores Jiménez-Farfán, Isabel Anaya-Rubio, Rosendo López-González, Guadalupe Palencia, Dora M. Frías-Márquez, Gerardo González-García, Carmen Rubio-Osornio, Minerva Calvillo-Velasco and Guadalupe Márquez-Chablé

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12875

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      Antiproliferative and apoptotic effect of bis(acetylacetonate-k2 O,O)(1,10-phenanthroline-k2 N,N)Zn(II) or Zn(acac)2(phen) complex was determined in several cancer cell lines. Acetylacetonate and phenanthroline ligands promote selectivity toward cancer cells.

    8. ‘Click’-xylosides as initiators of the biosynthesis of glycosaminoglycans: Comparison of mono-xylosides with xylobiosides

      Aurore Chatron-Colliet, Charlotte Brusa, Isabelle Bertin-Jung, Sandrine Gulberti, Nick Ramalanjaona, Sylvie Fournel-Gigleux, Stéphane Brézillon, Murielle Muzard, Richard Plantier-Royon, Caroline Rémond and Yanusz Wegrowski

      Version of Record online: 2 NOV 2016 | DOI: 10.1111/cbdd.12865

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      ‘Click’-xylosides displayed a better activity as primers of GAG biosynthesis than the corresponding xylobiosides with a better cellular uptake and affinity of β4GalT7.

    9. Construction of explicit models to correlate the structure and the inhibitory activity of aldose reductase: Flavonoids and sulfonyl-pyridazinones as inhibitors

      Fengchao Cui, Lunyang Liu, Haifeng Tang, Kecheng Yang and Yunqi Li

      Version of Record online: 31 OCT 2016 | DOI: 10.1111/cbdd.12868

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      Two explicit models are constructed to correlate the binding energies with the AR inhibitory activities of flavonoids and sulfonyl-pyridazinones. The introduction of multiple complex states can help the clarification of structure–activity relationship. The contribution from each energy term and the favorite of protein–inhibitor complex states are present. The accommodation of alternative binding sites for identical inhibitors at the presence/absence of coenzyme and substrate is observed.

  13. Review Articles

    1. Ebola virus: A gap in drug design and discovery - experimental and computational perspective

      Marissa Balmith, Mbuso Faya and Mahmoud E. S. Soliman

      Version of Record online: 31 OCT 2016 | DOI: 10.1111/cbdd.12870

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      There is a huge gap in literature with regard to the guidelines toward the discovery of anti-Ebola inhibitors. This review focuses on inhibitors of the Ebola virus, drug repurposing to combat Ebola, as well as in silico methods which study drug–target interactions. This report will be immensely valuable toward the design of Ebola virus inhibitors.

  14. Research Letters

    1. Berberine-loaded Janus nanocarriers for magnetic field-enhanced therapy against hepatocellular carcinoma

      Zheng Wang, Ying-shuai Wang, Zhi-min Chang, Li Li, Yi Zhang, Meng-meng Lu, Xiao Zheng, Mingqiang Li, Dan Shao, Jing Li, Li Chen and Wen-fei Dong

      Version of Record online: 26 OCT 2016 | DOI: 10.1111/cbdd.12866

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      We have developed Janus magnetic mesoporous silica nanoparticles (Fe3O4-mSiO2 NPs) with exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, pH-responsive drug release and low cytotoxicity for berberine (Ber) delivery. An external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3O4-mSiO2 NPs through enhancing berberine internalization. Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.

  15. Research Articles

    1. Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto-5′-nucleotidase

      Pervaiz Ali Channar, Syed Jawad Ali Shah, Sidra Hassan, Zaib un Nisa, Joanna Lecka, Jean Sévigny, Jürgen Bajorath, Aamer Saeed and Jamshed Iqbal

      Version of Record online: 26 OCT 2016 | DOI: 10.1111/cbdd.12861

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      Putative binding mode of compound 3j (colored green) in the human e5′NT crystal structure (brown) and 3g (magenta) in the rat e5′NT homology model (cyan).

    2. Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors

      Lu Liu, Muzammal Hussain, Jinfeng Luo, Anna Duan, Chaonan Chen, Zhengchao Tu and Jiancun Zhang

      Version of Record online: 17 OCT 2016 | DOI: 10.1111/cbdd.12863

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      Novel dasatinib analogues as DDR1 and DDR2 inhibitors were designed and synthesized. Some of the compounds showed the potent inhibitory activities against both DDR1 and DDR2, as well as anticancer activity in low nanomolar range against K562 cell line; especially, compound 3j demonstrated significantly better inhibitory potency than the parental dasatinib against both DDRs and also demonstrated the potent inhibitory activity against K562 cell lines.

    3. Design and characterization of short hybrid antimicrobial peptides from pEM-2, mastoparan-VT1, and mastoparan-B

      Hamed Memariani, Delavar Shahbazzadeh, Reza Ranjbar, Mahdi Behdani, Mojtaba Memariani and Kamran Pooshang Bagheri

      Version of Record online: 5 OCT 2016 | DOI: 10.1111/cbdd.12864

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      In this study, for the first time, a series of short hybrid antimicrobial peptides (SHAMPs) combined by different fragments of venom-derived α-helical antimicrobial peptides pEM-2, mastoparan-VT1 (MP-VT1), and mastoparan-B (MP-B) were designed. All peptides had membrane-disrupting activity in a time-dependent manner. Collectively, current study highlights the potential for rational design of improved SHAMPs such as PV3 that was an ideal candidate for further assessment with the ultimate purpose of development of effective antimicrobial agents.

    4. Synthesis, in vitro evaluation and molecular docking studies of novel coumarin-isatin derivatives as α-glucosidase inhibitors

      Guangcheng Wang, Jing Wang, Dianxiong He, Xin Li, Juan Li and Zhiyun Peng

      Version of Record online: 5 OCT 2016 | DOI: 10.1111/cbdd.12867

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      A new series of coumarin-isatin derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity. Among the newly derivatives, compound 5p was found to be the most active compound with IC50 values of 2.56 ± 0.08 μm. Molecular docking analysis revealed the existence of hydrophobic and hydrogen interactions between compound 5p and the active site of α-glucosidase.

    5. Structure-based discovery of novel US28 small molecule ligands with different modes of action

      Michael Lückmann, Roxana-Maria Amarandi, Natalia Papargyri, Mette H. Jakobsen, Elisabeth Christiansen, Lars J. Jensen, Aurel Pui, Thue W. Schwartz, Mette M. Rosenkilde and Thomas M. Frimurer

      Version of Record online: 28 SEP 2016 | DOI: 10.1111/cbdd.12848

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      The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor for various chemokines. Despite the recent determination of its 2.9 Å crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural information from a refined US28:VUF2274 complex for virtual screening of >12 million commercially available screening compounds. We tested 98 of the top 0.1% ranked compounds, revealing novel chemotypes with distinct pharmacological profiles – agonist and inverse agonist.

    6. Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties

      Anna M. Waszkielewicz, Karolina Słoczyńska, Elżbieta Pękala, Paweł Żmudzki, Agata Siwek, Anna Gryboś and Henryk Marona

      Version of Record online: 28 SEP 2016 | DOI: 10.1111/cbdd.12842

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      New xanthone derivatives were synthesized and evaluated for anticonvulsant properties and neurotoxicity in mice and rats. R,S-2-{2-[(1-hydroxybutan-2-yl]amino)ethoxy}-9H-xanthen-9-one and R,S-2-{3-[(1-hydroxybutan-2-yl)amino]propoxy}-9H-xanthen-9-one exerted activity in rats, p.o. 2 and 4 h after administration, respectively. Metabolic stability of the compounds was evaluated using rat microsomes, resulting in half-life t1/2 136 and 108 min, respectively.

    7. 1-[(Imidazolidin-2-yl)imino]-1H-indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies

      Anita Kornicka, Aleksandra Wasilewska, Jarosław Sączewski, Alan L. Hudson, Konrad Boblewski, Artur Lehmann, Karol Gzella, Mariusz Belka, Franciszek Sączewski, Maria Gdaniec, Apolonia Rybczyńska and Tomasz Bączek

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/cbdd.12846

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      1-[(Imidazolidin-2-yl)imino]-1H-indole analogues of a hypotensive α2-AR/imidazoline I1 binding site-selective ligand, 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (7-F-marsanidine), were synthesized and tested in vitro for α1- and α2-adrenergic and imidazoline I1 and I2 receptors’ binding affinities as well as in vivo for cardiovascular effects. 7-F-indole 3g, the most potent hypotensive agent in this series, is characterized by higher affinity and selectivity for α2-ARs over I1-IBS than that of 7-F-marsanidine. The newly prepared compounds are found to possess a high metabolic stability in vitro.

    8. Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents

      Hong-shun Gu, Xi Chen, Jian-wei Zhang, Lan Zhang and Lin Li

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/cbdd.12843

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      A series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities were evaluated by two models in vitro and two models in vivo. These results suggest that some of the synthesized compounds may have potential antipsychotic effect via inhibiting dopamine activity.

    9. Analysis of residue conformations in peptides in Cambridge structural database and protein-peptide structural complexes

      Upadhyayula Surya Raghavender

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/cbdd.12862

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      A statistical approach to studying peptide residue conformations in the crystal structures of protein-peptide complexes in PDB. A synthetic formulation to integrate structural information from CSD and PDB peptide structures is to derive chemically sensible density distributions for backbone conformations characterizing the flexibility of peptide residues.

    10. Synthesis and comparative in vivo evaluation of 99mTc(CO)3-labeled PEGylated and non-PEGylated cRGDfK peptide monomers

      Kusum Vats, Drishty Satpati, Rohit Sharma, Haladhar D. Sarma and Sharmila Banerjee

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/cbdd.12844

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      In this work two azide-modified PEGylated and non-PEGylated cRGDfK peptide monomers were clicked with propargyl glycine (Pra) to introduce a tridentate chelator for radiolabeling with [99mTc(CO)3(H2O)3]+ precursor. The non-PEGylated radiotracer, 99mTc(CO)3-Pra-Tz-CH2-cRGDfK showed higher tumor/blood, tumor/liver, tumor/kidney and tumor/lung ratios in comparison to the PEGylated radiotracer, 99mTc(CO)3-Pra-Tz-PEG7-cRGDfK.

    11. In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes

      Erika Ferrari, Rois Benassi, Monica Saladini, Giulia Orteca, Zuzana Gazova and Katarina Siposova

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/cbdd.12847

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      Curcumin analogues K2T demonstrated to inhibit Aβ1–40 fibrillization.

      K2T compounds act as copper(II) chelating agents reducing the free metal damage.

      K2T-Cu(II) complexes behave as DNA groove binders.


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