Chemical Biology & Drug Design

Cover image for Vol. 89 Issue 6

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 - 84

    1. Ligand recognition properties of the vasopressin V2 receptor studied under QSAR and molecular modeling strategies

      Marlet Martínez-Archundia, Brenda Colín-Astudillo, Liliana M. Moreno-Vargas, Guillermo Ramírez-Galicia, Ramón Garduño-Juárez, Omar Deeb, Martha Citlalli Contreras-Romo, Andres Quintanar-Stephano, Edgar Abarca-Rojano and José Correa-Basurto

      Version of Record online: 29 MAY 2017 | DOI: 10.1111/cbdd.13005

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      2D structure of conivaptan (left) and couple on V2R (right) for showing its chemical moieties as well as its recognition properties, respectively.

    2. Targeting on poly(ADP-ribose) polymerase activity with DNA-damaging hybrid lactam-steroid alkylators in wild-type and BRCA1-mutated ovarian cancer cells

      Dimitrios T. Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas and Vasiliki Sarli

      Version of Record online: 26 MAY 2017 | DOI: 10.1111/cbdd.13006

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      Conjugated lactam-steroid alkylators (LSA) have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemjournalapy. LSA produce anticancer activity through dual action by combining the direct induction of cellular DNA damage with the inhibition of PARP activity and consecutive DNA repair activity, as well as modulating PARP1/2 mRNA transcription. BRCA1-mutated UWB1.289 ovarian cancer cells with defective PARP-oriented repair mechanism show significantly higher sensitivity to these agents.

    3. Concluding the trilogy: The interaction of 2,2′-dihydroxy-benzophenones and their carbonyl N-analogues with human glutathione transferase M1-1 face to face with the P1-1 and A1-1 isoenzymes involved in MDR

      Nikolaos D. Georgakis, Dionisis A. Karagiannopoulos, Trias N. Thireou, Elias E. Eliopoulos, Nikolaos E. Labrou, Petros G. Tsoungas, Michael N. Koutsilieris and Yannis D. Clonis

      Version of Record online: 26 MAY 2017 | DOI: 10.1111/cbdd.13011

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      When the substrates CDNB and GSH (both in green) are bound to hGSTM1-1, 2,2’-dihydroxy-5-phenyl-benzophenone oxime (13) (in yellow) can still be accommodated in the binding pocket, effecting good inhibition. 13 is also a good inhibitor with hGSTA1-1 and a weaker one with hGSTP1-1, thus, qualifying as lead structure for designing hGST inhibitors.

    4. Virtual screening and biological evaluation of novel antipyretic compounds

      Thamires Quadros Froes, Miriam C. C. Melo, Gloria E. P. Souza, Marcelo Santos Castilho and Denis M. Soares

      Version of Record online: 25 MAY 2017 | DOI: 10.1111/cbdd.12995

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      It was developed a ligand-based pharmacophore model that differentiates true inhibitors from decoys and enlighten the structure–activity relationships for mPGES-1 inhibitors. Lead-like compounds were selected from ZINC database. Five compounds inhibited fever to LPS in rats. The most potent also reduced hypothalamic PGE2 production, without COX-1/2 inhibition.

    5. Preparation, characterization, and in vivo study of rhein solid lipid nanoparticles for oral delivery

      Haiyang Feng, Yuping Zhu, Zhixuan Fu and Dechuan Li

      Version of Record online: 25 MAY 2017 | DOI: 10.1111/cbdd.13007

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      In this study, rhein-SLNs were successfully produced by hot homogenization followed by ultrasonication. Precirol ATO5 in which rhein exhibited higher partition coefficient was selected for preparation of SLNs. In the dynamic light scattering, the rhein SLNs showed a smaller size with a mean value of 120.8 ± 7.9 nm and with zeta potential of −16.9 ± 2.3 mV. SLNs exhibited a good stability during the period of 2 months. The SLNs indicated faster drug release with a burst release within 2 hr and followed by a sustained release with a biphasic drug-release pattern. Comparing with the same concentration (free drug), the cellular cytotoxicity of rhein-loaded SLNs increased significantly at the same incubation condition. In vivo, the AUC0-t of rhein in the form of SLNs was significantly increased and was 2.06-fold that of suspensions group. The results showed an increased oral absorption and improved the oral bioavailability of rhein by the formulation of SLNs.

    6. Identification of indothiazinone as a natural antiplatelet agent

      Chansik Yang, Sugyeong Kwon, Se-Jong Kim, Minseon Jeong, Ji-Young Park, Dongeun Park, Soon Jun Hong, Jong-Wha Jung and Chungho Kim

      Version of Record online: 25 MAY 2017 | DOI: 10.1111/cbdd.13008

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      Indothiazinone, a natural product from myxobacteria, was shown to inhibit agonist-induced platelet spreading by suppressing talin-mediated integrin αIIbβ3 activation. This study also shows that indothiazinone can be used as a lead compound in the development of antiplatelet drugs with a novel mode of action.

    7. Design and development of some thiazole-based flavanoids as novel antibacterial against pathogens causing surgical site infection for possible benefit in bone trauma via inhibition of DNA gyrase

      Gang Zhao, Dengzhe Lan and Guobao Qi

      Version of Record online: 22 MAY 2017 | DOI: 10.1111/cbdd.12999

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      Novel class of hybrid thiazole-based flavanoids derivatives have been synthesized and evaluated for antibacterial activity for possible benefit in bone trauma via inhibition of DNA gyrase enzyme.

    8. Deleterious effects of non-synonymous single nucleotide variants of human IL-1β gene

      Yue-Hui Zhang, Jia Song, Jing Zhang and Jiang Shao

      Version of Record online: 22 MAY 2017 | DOI: 10.1111/cbdd.12976

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      The IL-1β is currently a hot molecule in IDD research, and the effects of its nsSNVs are studied here. Based on the constructed 3D structure of pro-IL-1β, F162S was proposed to reduce stability of pro-IL-1β protein with multiple analyses. While based on the experimental 3D structure of mature IL-1β and its neutralizing McAb canakinumab complex, L31F was found to attenuate the interaction of IL-1β with canakinumab by reducing binding energy, while F162S could not.

    9. You have full text access to this OnlineOpen article
      tRF-Leu-CAG promotes cell proliferation and cell cycle in non-small cell lung cancer

      Yang Shao, Qiangling Sun, Xiaomin Liu, Ping Wang, Renqi Wu and Zhongliang Ma

      Version of Record online: 22 MAY 2017 | DOI: 10.1111/cbdd.12994

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      tRF-Leu-CAG RNA levels were higher in NSCLC tumor tissues than in normal tissues, and also upregulated in NSCLC cell lines. A significant relationship was observed between stage progression and tRF-Leu-CAG in NSCLC sera. We found that in H1299 cells, inhibition of tRF-Leu-CAG suppressed cell proliferation and impeded cell cycle, and AURKA was also repressed with the knockdown of tRF-Leu-CAG.

    10. Toward the rational design of macrolide antibiotics to combat resistance

      Anna Pavlova, Jerry M. Parks, Adegboyega K. Oyelere and James C. Gumbart

      Version of Record online: 16 MAY 2017 | DOI: 10.1111/cbdd.13004

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      The molecular causes of resistance to macrolide antibiotics by bacterial ribosomes are examined with MD simulations. Novel macrolide derivatives exploiting a conserved, functionally relevant interaction are also explored, and suggestions for further improvement are given.


    1. Therapeutic potential of chemically modified siRNA: Recent trends

      Chelliah Selvam, Daniel Mutisya, Sandhya Prakash, Kasturi Ranganna and Ramasamy Thilagavathi

      Version of Record online: 16 MAY 2017 | DOI: 10.1111/cbdd.12993

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      Ribose Modifications, Phosphate Backbone Modifications, Nucleobase Modifications, Modification to the Termini and Conjugate groups, siRNA Binding.


    1. Identification of natural inhibitors of Bcr-Abl for the treatment of chronic myeloid leukemia

      Phanikrishna Parcha, Sailu Sarvagalla, Bindu Madhuri, Sankar Pajaniradje, Vinitha Baskaran, Mohane Selvaraj Coumar and Baskaran Rajasekaran

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.12983

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      In this study, we performed virtual screening of ZINC natural compounds by docking to the Abl kinase ATP-binding site using Glide software. Two natural inhibitors ZINC08764498 (hit1) and ZINC12891610 (hit2) were selected by considering their high Glide docking score and stable interaction with the hinge region residue Met-318 of Abl kinase catalytic domain. The compounds were further validated using density functional theory and 10-ns molecular dynamic simulations. In vitro testing results showed that compound ZINC08764498 (hit1) has selective pro-apoptotic activity on Bcr-Abl-overexpressing K-562 cells and no significant cytotoxicity on Bcr-Abl-negative HEK-293 cell line.

    2. Novel antimicrobial peptide CPF-C1 analogs with superior stabilities and activities against multidrug-resistant bacteria

      Junqiu Xie, Qian Zhao, Sisi Li, Zhibin Yan, Jing Li, Yao Li, Lingyun Mou, Bangzhi Zhang, Wenle Yang, Xiaokang Miao, Xianxing Jiang and Rui Wang

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.12988

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      To improve the stability of the natural antimicrobial peptide CPF-C1, a series of analogs were designed and synthesized by chemical modification. Among the analogs, CPF-9 was notable due to its greater antimicrobial potency in vitro and in vivo and its superior stability, lower hemolytic activity, and higher antibiofilm activity. It killed bacteria not only by disrupting the bacterial membranes but also by binding to DNA. This analog is a potential antibiotic candidate for treating infections induced by multidrug-resistant bacteria.

  4. Research Articles

    1. The anti-Trichomonas vaginalis phloroglucinol derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis

      Camila Braz Menezes, Graziela Vargas Rigo, Henrique Bridi, Danielle da Silva Trentin, Alexandre José Macedo, Gilsane Lino von Poser and Tiana Tasca

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.13002

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      The phloroglucinol derivative of Hypericum species, isoaustrobrasilol B, was active against T. vaginalis. It significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the influence of extracellular nucleotide accumulation on immune mechanisms was evaluated revealing enhanced IL-8 levels in T. vaginalis-stimulated neutrophils. The associative effect of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to neutrophils consequently, contributing to parasite clearance.


    1. A comparison inhibitory effects of cisplatin and MNPs-PEG-cisplatin on the adhesion capacity of bone metastatic breast cancer

      Mohammad Javad Mokhtari, Fatemeh Koohpeima and Hadi Mohammadi

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.12985

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      A new formulation of cisplatin loaded onto Fe3O4MNPs-PEG has been synthesized and characterized. The in vitro evaluation of the study found that cisplatin and cisplatin-loaded MNPs-PEG decreased the rate of metastasis, migration, and adhesion of T47D to distant organs. MNPs-PEG-cisplatin strongly increased anti-cancer effects compared with free cisplatin in the T47D cell line.

    2. A field-based disparity analysis of new 1,2,5-oxadiazole derivatives endowed with antiproliferative activity

      Federica Porta, Arianna Gelain, Daniela Barlocco, Nicola Ferri, Silvia Marchianò, Valentina Cappello, Livia Basile, Salvatore Guccione, Fiorella Meneghetti and Stefania Villa

      Version of Record online: 14 MAY 2017 | DOI: 10.1111/cbdd.13003

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      New 1,2,5-oxadiazoles were synthesized as new potential antiproliferative agents. The field-based disparity analysis highlighted the relevance of the negative electrostatic field on the heterocyclic core for activity. The SAR provided can be exploited to carry out further lead optimization.

    3. Exploring the RNA-bound and RNA-free human Argonaute-2 by molecular dynamics simulation method

      Ren Kong, Lei Xu, Lianhua Piao, Dawei Zhang, Ting-Jun Hou and Shan Chang

      Version of Record online: 12 MAY 2017 | DOI: 10.1111/cbdd.12997

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      Large conformational changes were detected in hAgo2-free system comparing to RNA bounded hAgo2, especially for PAZ domain. The reorientation of PAZ domain not only influences the binding of helix-7 and RNA duplex, the initial pairing process, but also the shape of N-PAZ cleft, where the supplemental base pairing occurs. We speculate that PAZ domain played important role in hAgo2-mediated miRNA-induced gene regulation.

    4. Docking-based design and synthesis of galantamine–camphane hybrids as inhibitors of acetylcholinesterase

      Georgi Stavrakov, Irena Philipova, Dimitrina Zheleva-Dimitrova, Iva Valkova, Evdokiya Salamanova, Spiro Konstantinov and Irini Doytchinova

      Version of Record online: 12 MAY 2017 | DOI: 10.1111/cbdd.12991

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      The galantamine fragment of the galantamine–camphane hybrids bind the catalytic site of acetylcholinesterase, while the camphane fragment fits in the peripheral anionic site, where the Ω-loop of amyloid beta peptide binds to the enzyme. The inhibitor “closes” the binding site by causing a shift of Trp286 and prevents the amyloid beta peptide from binding.

    5. Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold

      Dezhi Yang, Dongdong Tong, Qian Zhang, Yongtao Wang, Jing Sun, Fenghe Zhang and Guisen Zhao

      Version of Record online: 7 MAY 2017 | DOI: 10.1111/cbdd.13000

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      A novel series of indole derivatives targeting the Akt1 were designed and synthesized. Compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at the concentration of 10 nm and fivefold higher antiproliferative activity against PC-3 cell with IC50 value of 3.1 ± 0.1 μm than positive control (15.5 ± 0.4 μm).

    6. Live cell imaging of bacterial cells: Pyrenoylpyrrole-based fluorescence labeling

      Mathiyazhagan Arun Divakar and Sivakumar Shanmugam

      Version of Record online: 7 MAY 2017 | DOI: 10.1111/cbdd.12978

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      Novel pyrenoylpyrrole compounds were synthesized from easily available synthons. All the compounds were non-cytotoxic, potential candidates for microbial cell imaging to aid diagnostics with moderate antibacterial activity.

    7. Reprofiling of full-length phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides toward antiproliferative agents: Synthesis, antiproliferative activity, and molecular docking study

      Majdi M. Bkhaitan, Agha Zeeshan Mirza, Ashraf N. Abdalla, Hina Shamshad, Zaheer Ul-Haq, Mohammed Alarjah and Anna Piperno

      Version of Record online: 7 MAY 2017 | DOI: 10.1111/cbdd.12987

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      Series of phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides were synthesized and evaluated for their in vitro antiproliferative activity against MCF-7, A2780, HCT116, and MRC5 using MTT assay. Molecular docking confirmed high affinity to two different receptors for anticancer nucleosides namely 1P5Z and 2ZIA. ADME was predicted through a theoretical kinetic study.


    1. Syntheses and structure–membrane active antimicrobial activity relationship of alkylamino-modified glucose, maltooligosaccharide, and amylose

      Hatsuo Yamamura, Takahiro Mabuchi, Tomoki Ishida and Atsushi Miyagawa

      Version of Record online: 6 MAY 2017 | DOI: 10.1111/cbdd.12989

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      Alkylamine-modified sugars prepared via a microwave-assisted click reaction exhibited a unique relationship of their bacterial membrane permeabilization and antimicrobial activity with the number of functional groups and the size and shape of the molecular scaffold.


    1. Antibacterial and antitubercular evaluation of dihydronaphthalenone-indole hybrid analogs

      Praveen Kumar V, Renjitha J, Fathimath Salfeena C T, Ashitha K T, Rangappa S. Keri, Sunil Varughese and Sasidhar Balappa Somappa

      Version of Record online: 6 MAY 2017 | DOI: 10.1111/cbdd.12990

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      Sc(OTf)3 catalyzed Michael addition of indoles to the arylidene/hetero arylidene ketones. Compounds 5l, 5o, and 5p demonstrated MIC of 3.12 µg/ml against E. coli and S. aureus. Compounds 5o and 5p demonstrated MIC of 6.25 µg/ml against M. tuberculosis. Our studies complement new and exciting findings which strongly suggest that the indolyl naphthalenones have real potential in finding suitable “Leads” for development of antitubercular therapeutics.

    2. Novel 19F-MRS β-galactosidase reporter molecules incorporated nitrogen mustard analogues

      Zijun Yu, Jianru Zhao, Zhiming Hua, Xinping Wang, Xiaobo Wang, Hanqin Wang and Jian-Xin Yu

      Version of Record online: 6 MAY 2017 | DOI: 10.1111/cbdd.12992

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      A novel molecular platform integrated fluorinated antitumor nitrogen mustards for 19F-MRS assay of β-galactosidase activity was proposed. Accordingly, we designed, synthesized and characterized a series of fluorinated nitrogen mustards 19F-MRS reporter molecules, and found that 2-fluoro-4-[bis(2'-chloroethyl)amino]phenyl β-D-galactopyranoside 5 was very sensitive (n=738.4mM/min/unit) to β-gal (E801A) in PBS at 37°C with DdF=3.79ppm, demonstrating the feasibility of this molecular platform by further assessment of β-gal activity in vitro with lacZ transfected human MCF7 breast and PC3 prostate tumor cells.


    1. Epidermal growth factor receptor (EGFR) structure-based bioactive pharmacophore models for identifying next-generation inhibitors against clinically relevant EGFR mutations

      Pooja S. Panicker, Anu R. Melge, Lalitha Biswas, Pavithran Keechilat and Chethampadi G. Mohan

      Version of Record online: 3 MAY 2017 | DOI: 10.1111/cbdd.12977

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      EGFR and its mutants showed resistance to FDA approved drugs. Development of EGFR and its mutant structure based e-pharmacophore model for virtual screening of drug like molecules. CUDC101 and ML167 can be a potent EGFR inhibitor overcoming its mutant resistance. Developed 3D e-pharmacophore models can be used for identifying new scaffold-based molecules.


    1. The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel

      Patrícia S. Guerreiro, Eduardo Corvacho, João G. Costa, Nuno Saraiva, Ana S. Fernandes, Matilde Castro, Joana P. Miranda and Nuno G. Oliveira

      Version of Record online: 3 MAY 2017 | DOI: 10.1111/cbdd.12979

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      The human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional DNA repair enzyme with relevant redox signalling functions. The quinone derivative E3330, a redox inhibitor of APE1, decreased the colony formation and chemoinvasion of docetaxel-treated MDA-MB-231 cells (represented in blue). In addition, E3330 as single agent (represented in red) significantly reduced the collective cell migration. These results suggest APE1 redox function as a potential target for the modulation of cell migration and invasion in metastatic breast cancer.


    1. New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum

      Marina T. Varela, Marta L. Lima, Mariana K. Galuppo, Andre G. Tempone, Alberto de Oliveira, João Henrique G. Lago and João Paulo S. Fernandes

      Version of Record online: 3 MAY 2017 | DOI: 10.1111/cbdd.12986

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      Alkenylbenzene molecules isolated from Piper malacophyllum have shown promising antiparasitic activity and low cytotoxicity. Several synthetic analogues were prepared to optimize the activity against Trypanosoma cruzi and Leishmania infantum. The amine analogues were the most promising.


    1. Rational drug design of indazole-based diarylurea derivatives as anticancer agents

      Yan-yan Chu, He-juan Cheng, Zhen-hua Tian, Jian-chun Zhao, Gang Li, Yang-yang Chu, Chang-jun Sun and Wen-bao Li

      Version of Record online: 2 MAY 2017 | DOI: 10.1111/cbdd.12984

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      Based on the structure-based drug design, we designed and prepared a series of novel indazole-based diarylurea derivatives targeting c-kit, and their antiproliferative activities were evaluated. We used molecular docking method to explore the interaction mechanisms and SAR. Compound 1i possessed improved solubilities and best activities. It is a promising anticancer agent and under further development.

    2. N-hydroxy-substituted 2-aryl acetamide analogs: A novel class of HIV-1 integrase inhibitors

      Utsab Debnath, Prachi Kumar, Aakanksha Agarwal, Ajay Kesharwani, Satish K. Gupta and Seturam B. Katti

      Version of Record online: 26 APR 2017 | DOI: 10.1111/cbdd.12974

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      Based on an in silico approach, novel classes of N-hydroxy-substituted 2-aryl acetamide analogues were identified as anti-HIV-1 integrase inhibitors. To do that, de novo-designed molecules were chemically and biologically evaluated to find out a hit (compound 4b). The structure of compound 4b was further optimized for better binding affinity toward the integrase binding pocket. Finally, biological evaluation followed by docking studies revealed compounds 6–2c and 6–5b as new leads of HIV-1 integrase inhibitors.

    3. Piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates: Synthesis and antiplasmodial evaluation

      Amandeep Singh, Anu Rani, Jiri Gut, Philip J. Rosenthal and Vipan Kumar

      Version of Record online: 26 APR 2017 | DOI: 10.1111/cbdd.12982

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      Synthesis of piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates and their evaluation against chloroquine-resistant and mefloquine-sensitive W2 strain of Plasmodium falciparum.


    1. Biological screening of cucurbitacin inspired estrone analogs targeting mitogen-activated protein kinase (MAPK) pathway

      Mahmoud S. Ahmed, Fardous El-Senduny, Jessica Taylor and Fathi T. Halaweish

      Version of Record online: 25 APR 2017 | DOI: 10.1111/cbdd.12963

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      Azide functional moiety was installed across 23, 24 α, β-unsaturated ketone side chain to mimic cucurbitacin skeleton. MH-4 exhibited significant antiproliferative activity against A-375 cell lines (3.60 µm) and significant inhibition of p-ERK levels.


    1. Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates

      Travis Korosh, Emmanuel Bujans, Mary Morada, Canan Karaalioglu, Jean Jacques Vanden Eynde, Annie Mayence, Tien L. Huang and Nigel Yarlett

      Version of Record online: 25 APR 2017 | DOI: 10.1111/cbdd.12972

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      A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10H20) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates. Compound 3m, 2,2′-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, had good in vitro (9 μm) and in vivo (25 mg/kg per day for 4 days) activity. Compound 3m was reduced by pyruvate:ferredoxin oxidoreductase by a ferredoxin independent mechanism.

    2. Modified benzoxazolone derivative as 18-kDa TSPO ligand

      Neelam Kumari, Nidhi Chadha, Pooja Srivastava, Lokesh Chandra Mishra, Sunita Bhagat, Anil K. Mishra and Anjani K. Tiwari

      Version of Record online: 19 APR 2017 | DOI: 10.1111/cbdd.12971

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      A new congener of acetamidobenzoxazolone called as NBMP or 2-[5 (naphthyl)amino-2-oxobenzo-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-penylacetamide has shown 10.8 ± 1.2 nm binding affinity towards TSPO under in vitro conditions.

    3. Design, synthesis, biological evaluation, and molecular docking of novel flavones as H3R inhibitors

      Gang Wen, Qian Liu, Huabin Hu, Dongmei Wang and Song Wu

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12981

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      A series of novel flavone derivatives were designed, synthesized, and evaluated for their H3R inhibitory activity. To elucidate the interactions between compounds and H3R, we built a homology model of H3R and performed molecular docking studies.

    4. Synthesis, in vitro evaluation, and 68Ga-radiolabeling of CDP1 toward PET/CT imaging of bacterial infection

      Jyotibon Dutta, Sooraj Baijnath, Anou M. Somboro, Savania Nagiah, Fernando Albericio, Beatriz G. de la Torre, Biljana Marjanovic-Painter, Jan Rijn Zeevaart, Mike Sathekge, Hendrik G. Kruger, Anil Chuturgoon, Tricia Naicker, Thomas Ebenhan and Thavendran Govender

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12980

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      A bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) was utilized to functionalize the antimicrobial peptide, which in turn was capable of chelating gallium. The synthesized natGa-CDP1 showed bacterial selectivity and low affinity toward hepatic cells, which are favorable characteristics for further preclinical application.

    5. Design, synthesis, and in vitro antituberculosis activity of benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4-oxadiazole derivatives

      Yasodakrishna Sajja, Sowmya Vanguru, Hanmanth Reddy Vulupala, Lingaiah Nagarapu, Yogeswari Perumal, Dharmarajan Sriram and Jagadeesh Babu Nanubolu

      Version of Record online: 17 APR 2017 | DOI: 10.1111/cbdd.12969

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      Benzo[6,7]cyclohepta[1,2-b]pyridine-1,3,4-oxadiazole hybrids (4a–o) were synthesized using di(acetoxy)iodobenzene-mediated oxidative cyclization. All the synthesized compounds 4(a–o) were screened for their in vitro antitubercular activity against M. tuberculosis H37Rv (ATCC 27294) by using agar dilution method. Compounds 4o, 4l, and 4m were found to be more active than standard drug ethambutol and have shown lower cytotoxicity.

    6. Quantitative structure–activity relationship and molecular docking studies on designing inhibitors of the perforin

      Fucheng Song, Lianhua Cui, Jinmei Piao, Hui Liang, Hongzong Si, Yunbo Duan and Honglin Zhai

      Version of Record online: 12 APR 2017 | DOI: 10.1111/cbdd.12975

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      The molecular docking analysis of compound 42a shows a detailed binding mode with three hydrogen bond interactions (red dashes) formed with residues TRP-112 and ASP-132.

    7. New liposomal doxorubicin nanoformulation for osteosarcoma: Drug release kinetic study based on thermo and pH sensitivity

      Fateme Haghiralsadat, Ghasem Amoabediny, Mohammad Hasan Sheikhha, Behrouz Zandieh-doulabi, Samira Naderinezhad, Marco N. Helder and Tymour Forouzanfar

      Version of Record online: 12 APR 2017 | DOI: 10.1111/cbdd.12953

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      In this study, we presented the novel simple targeting for PEGylated liposomal formulation with an appropriate mean size of vesicle, encapsulation efficiency, PDI, zeta potentials in order to osteosarcoma treatment. We also employed novel comprehensive formulation to help researchers.

    8. One-pot cascade synthesis and in vitro evaluation of anti-inflammatory and antidiabetic activities of S-methylphenyl substituted acridine-1,8-diones

      Lavanya Mallu, Dhakshanamurthy Thirumalai and Indira Viswambaran Asharani

      Version of Record online: 12 APR 2017 | DOI: 10.1111/cbdd.12973

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      One-pot cascade reaction of 4-(methylthio)benzaldehyde and dimedone with various amines afforded S-methylphenyl substituted acridine-1,8-diones in ethanol.

    9. Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway

      Liangyu Zhang, Zelong Fu, Xia Li, Haitao Tang, Jiesi Luo, Dehui Zhang, Yongzhi Zhuang, Zhiyang Han and Mingzhu Yin

      Version of Record online: 11 APR 2017 | DOI: 10.1111/cbdd.12965

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      The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. We reported that the activation of TAK1-p38 MAPK cascade is associated with the formation and cell proliferation of the TNBC. The inhibition of the TAK1 activity could be a specific and promising biomarker and target for anticancer diagnosis or treatment for TNBC.

    10. The NmrA-like family domain containing 1 pseudogene Loc344887 is amplified in gallbladder cancer and promotes epithelial–mesenchymal transition

      Xiao-Cai Wu, Shou-hua Wang, Hong-hui Ou, Bing Zhu, Yong Zhu, Qi Zhang, Yang Yang and Hua Li

      Version of Record online: 11 APR 2017 | DOI: 10.1111/cbdd.12967

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      Loc344887 is significantly upregulated in gallbladder cancer samples. Downregulation of Loc344887 in GBC cells suppressed cell proliferation. Loc344887 promotes epithelial-to-mesenchymal-transition in GBC cells.

    11. MD simulations and multivariate studies for modeling the antileishmanial activity of peptides

      Mirian Elisa Rodrigues Guerra, Valmir Fadel, Vinícius Gonçalves Maltarollo, Gisele Baldissera, Kathia Maria Honorio, José Roberto Ruggiero and Marcia Perez dos Santos Cabrera

      Version of Record online: 8 APR 2017 | DOI: 10.1111/cbdd.12970

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      A quantitative structure–activity relationship model was constructed for predicting the antileishmanial activity of peptides through an innovative theoretical approach. Molecular descriptors were prospected from physicochemical properties and from parameters of the folded peptide chains, calculated after molecular dynamics simulations in a membrane-mimetic environment. They were used as input for the model generation, which predicts that cationic charge, backbone solvation, solvent-accessible surface area, and volume are important for activity.

    12. Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives

      Glaécia A. N. Pereira, Gisele C. Souza, Lourivaldo S. Santos, Lauro E. S. Barata, Carla C. F. Meneses, Antoniana U. Krettli, Cláudio Tadeu Daniel-Ribeiro and Cláudio Nahum Alves

      Version of Record online: 6 APR 2017 | DOI: 10.1111/cbdd.12968

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      Synthesis and docking studies of new neolignan derivatives with antimalarial activity.

    13. siRNA-loaded liposomes: Inhibition of encystment of Acanthamoeba and toxicity on the eye surface

      Kathrin Faber, Giovanni K. Zorzi, Nathalya T. Brazil, Marilise B. Rott and Helder F. Teixeira

      Version of Record online: 4 APR 2017 | DOI: 10.1111/cbdd.12958

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      Glycogen phosphorylase, a key enzyme for encystment of Acanthamoeba, was silenced. PEGylated cationic liposomes were used as carriers for siRNA delivery. There was a significant reduction in the encystment of AP2 trophozoites.

    14. Novel nucleoside analogues targeting HCV replication through an NS5A-dependent inhibition mechanism

      Nikolaos Lougiakis, Efseveia Frakolaki, Panagiota Karmou, Nicole Pouli, Panagiotis Marakos, Vanesa Madan, Ralf Bartenschlager and Niki Vassilaki

      Version of Record online: 24 MAR 2017 | DOI: 10.1111/cbdd.12966

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      A number of new tricyclic nucleosides were synthesized and their inhibitory potential against HCV was evaluated. The benzylamino derivative 15d reduced HCV replication and possessed selectivity index 4.97 in 1b genotype. Resistance mutation studies were performed, suggesting that this compound could possess a NS5A-dependent mechanism of action, which is unexpected for nucleoside derivatives.

    15. Structure-based derivation of peptide inhibitors to target TGF-β1 receptor for the suppression of hypertrophic scarring fibroblast activation

      Huan Hu, Songlin Yang, Jianghong Zheng and Guangyu Mao

      Version of Record online: 24 MAR 2017 | DOI: 10.1111/cbdd.12954

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      A structure-based approach is described to derive peptide inhibitor from the complex interface of TGF-β1 with TβRII. The peptide is extended and cyclized by introducing a disulfide bond across its terminal residues. Computational analysis and fluorescence-based assay suggest that the cyclization can largely reduce the peptide flexibility and considerably minimize entropy penalty upon the peptide binding to TβRII.

    16. Radiolabeling, quality control, and biological characterization of 177Lu-labeled kanamycin

      Muhammad Usman Akbar, Tanveer Hussain Bokhari, Muhammad Khalid, Muhammad Razeen Ahmad, Samina Roohi, Saira Hina, Sajid Mehmood, Muhammad Sohaib and Tania Jabbar

      Version of Record online: 15 MAR 2017 | DOI: 10.1111/cbdd.12960

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      99mTc-kanamycin, used for bacterial infection imaging, is short-lived and cannot be transported over long distances. To resolve this, kanamycin was labeled with lutetium-177, a long-lived isotope that emits β- and γ-radiation. Radiolabeling of 177Lu-kanamycin was optimized. 177Lu-kanamycin was prepared with a very high yield (~100%) and showed excellent stability in vitro. Biodistribution and scintigraphy studies in mice and rabbit showed rapid clearance from body, suggesting that 177Lu-kanamycin could be used for medical imaging.

    17. Synthesis and characterization of a novel series of 1,4-dihydropyridine analogues for larvicidal activity against Anopheles arabiensis

      Bhaskara D. Dharma Rao, Subhrajyoti Bhandary, Deepak Chopra, Katharigatta N. Venugopala, Raquel M. Gleiser, Kabange Kasumbwe and Bharti Odhav

      Version of Record online: 11 MAR 2017 | DOI: 10.1111/cbdd.12957

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      The title compounds were synthesized by a one-pot multi-component Hantzsch ester synthesis in aqueous medium under catalyst-free conditions. Larvicidal results revealed that the presence of different substituents, namely nitro, chloro, and methoxy groups, influenced the larvicidal activity when compared to the standard compound. A promising larvicidal compound from the series has been characterized using single crystal X-ray diffraction.

    18. Controlled release of an endostatin peptide using chitosan nanoparticles

      Sanaz Ebrahimi Samani, Zahra Seraj, Hossein Naderimanesh, Khosro Khajeh, Ahmad Reza Esmaeili Rastaghi, Taher Droudi, Peirhosein Kolivand, Hadi Kazemi and S. Mohsen Asghari

      Version of Record online: 11 MAR 2017 | DOI: 10.1111/cbdd.12959

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      Application of anticancer peptides is limited by fast elimination from the systemic circulation. In this study, chitosan nanoparticles are used for the controlled release of an engineered antiangiogenic peptide derived from the N-terminal fragment of human endostatin. The nanoparticles were characterized before and after peptide loading by FTIR, zeta sizer and SEM. Our measurements revealed that chitosan nanoparticles are able to adsorb the peptide as ~70% and complete release took place after 80 h. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than cancer cell lines. These results underscore the promise of chitosan nanoparticles as therapeutics nanosystems.

    19. Investigation of the bindings of a class of inhibitors with GSK3β kinase using thermodynamic integration MD simulation and kinase assay

      Chia-Jen Hsu, Wen-Chi Hsu, Der-Jay Lee, An-Lun Liu, Chia-Ming Chang, Huei-Jhen Shih, Wun-Han Huang, Guey-Jen Lee-Chen, Hsiu Mei Hsieh-Li, Guan-Chiun Lee and Ying-Chieh Sun

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12946

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      GSk3β kinase is an important protein target for several diseases. Finding new small-molecule inhibitors may yield new lead compounds, and spur drug discovery. Based on an existing ligand–GSK3β kinase complex structure, thermodynamic integration MD simulation was utilized to investigate binding for a class of analogous compounds. The binding affinities of three new selected compounds were measured using a kinase assay. This article reports the binding affinities and predicted binding modes of these compounds.

    20. Molecular basis for covalent inhibition of glyceraldehyde-3-phosphate dehydrogenase by a 2-phenoxy-1,4-naphthoquinone small molecule

      Stefano Bruno, Elisa Uliassi, Mirko Zaffagnini, Federica Prati, Christian Bergamini, Riccardo Amorati, Gianluca Paredi, Marilena Margiotta, Paola Conti, Maria Paola Costi, Marcel Kaiser, Andrea Cavalli, Romana Fato and Maria Laura Bolognesi

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12941

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      Herein, using multiple chemical and biological approaches and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) orthologs, we report on the ability of 2-phenoxy-1,4-naphthoquinone (1) to act as a covalent GAPDH inhibitor, by a cysteine trapping mechanism. Chemical probes 24 allowed us to further investigate the proposed mechanism of interaction. Moreover, we preliminarily evaluated the selectivity of 1 over other two thiol-dependent enzymes, supporting its suitability as a warhead fragment for GAPDH inhibitor design.

    21. In silico analysis of the deleterious nsSNPs (missense) in the homeobox domain of human HOXB13 gene responsible for hereditary prostate cancer

      Gopalakrishnan Chandrasekaran, Eu Chang Hwang, Taek Won Kang, Dong Deuk Kwon, Kwangsung Park, Je-Jung Lee and Vinoth-Kumar Lakshmanan

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12938

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      In silico analysis and screening of the nsSNPs present in the DNA-binding domain (homeobox) of human HOXB13 gene is of crucial importance, since nsSNPs are known to be the prime cause for hereditary prostate cancer. Further, in silico protein mutation studies and subsequent validation by Ramachandran plot revealed P222R, G216C, W263R, and K218R to render serious damaging effects on the HOXB13 protein structure, stability, and function. However, the exact mechanism and pathology of these nsSNPs should be studied in depth in vitro/ in vivo.

  14. Research Articles

    1. Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents

      Hua-Li Qin, Jing Leng, Bahaa G. M. Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Muhammad Ajaz Hussain, Zahid Hussain, Syeda Naveed Kazmi and Syed Nasir Abbas Bukhari

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12964

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      Newly synthesized oxime analogs showed strong antiproliferative activity against the cancer cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAFV600E were also investigated.


    1. NMR structure-based optimization of Staphylococcus aureus sortase A pyridazinone inhibitors

      Albert H. Chan, Sung Wook Yi, Ethan M. Weiner, Brendan R. Amer, Christopher K. Sue, Jeff Wereszczynski, Carly A. Dillen, Silvia Senese, Jorge Z. Torres, J. Andrew McCammon, Lloyd S. Miller, Michael E. Jung and Robert T. Clubb

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12962

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      NMR spectroscopy was used to determine the structure of Staphylococcus aureus sortase A transpeptidase enzyme in complex with a pyridazinone-based small molecule, a potential anti-infective agent. Computational and synthetic chemistry methods led to second-generation analogs that are 70-fold more potent than the lead molecule, less cytotoxic and effective at impairing sortase A-mediated protein display on the surface of S. aureus. These pyridazinone analogues are attractive candidates for further development into anti-infective agents.

    2. A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells

      Zelal Adiguzel, Seniz Ozalp-Yaman, Gokalp Celik, Safia Salem, Tugba Bagci-Onder, Filiz Senbabaoglu, Yüksel Cetin and Ceyda Acilan

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12940

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      A novel Pt-blue complex induces DNA damage leading to apoptosis through oxidative stress and elevation of proapoptotic proteins in cancer cells.

    3. Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways

      Adriane F. Brito, James O. Fajemiroye, Hiasmin F. S. Neri, Dayane M. Silva, Daiany P. B. Silva, Germán Sanz, Boniek G. Vaz, Flávio S. de Carvalho, Paulo C. Ghedini, Luciano M. Lião, Ricardo Menegatti and Elson A. Costa

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/cbdd.12961

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      LQFM032 showed anxiolytic-like activity without motor impairment. anxiolytic-like activity of LQFM032 was antagonized by flumazenil and mecamylamine; LQFM032 did not alter mnemonic activity.

    4. Importance of functional groups in predicting the activity of small molecule inhibitors for Bcl-2 and Bcl-xL

      Vishnupriya Kanakaveti, Ramasamy Sakthivel, S. K. Rayala and M. Michael Gromiha

      Version of Record online: 1 MAR 2017 | DOI: 10.1111/cbdd.12952

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      Developed scaffold-specific models for predicting Bcl-2 and Bcl-xL small molecule inhibitors. Explored the important functional groups affecting BH3 mimicking. Hydrogen bonding, flexibility, volume and surface area of atoms are vital for BH3 mimicking. Designed a Web server for predicting the activity of novel compounds. Screened novel compounds for all the seven scaffolds.

    5. A novel mitochondria-targeting fluorescent probe for hydrogen sulfide in living cells

      Wei Shi, Miaobo Pan, Hao Qiang, Qianqian Qiu, Wenlong Huang, Haiyan Lin, Hai Qian and Liang Ge

      Version of Record online: 28 FEB 2017 | DOI: 10.1111/cbdd.12948

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      A novel mitochondria-targeting fluorescent probe compound S-N3 as the monitor of hydrogen sulfide (H2S) in living cells has been designed and synthesized in this study.

  16. Research Articles

    1. Design, synthesis, biological evaluation, and 3D-QSAR analysis of podophyllotoxin–dioxazole combination as tubulin targeting anticancer agents

      Zi-Zhen Wang, Wen-Xue Sun, Xue Wang, Ya-Han Zhang, Han-Yue Qiu, Jin-Liang Qi, Yan-Jun Pang, Gui-Hua Lu, Xiao-Ming Wang, Fu-Gen Yu and Yong-Hua Yang

      Version of Record online: 28 FEB 2017 | DOI: 10.1111/cbdd.12942

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      It proves that compound 7c conjugated in the colchicine site of tubulin (1SA0) perfectly and cyclin A2 and CDK2 are involved in the cell cycle process induced by 7c.


    1. Virtual screening, SAR, and discovery of 5-(indole-3-yl)-2-[(2-nitrophenyl)amino] [1,3,4]-oxadiazole as a novel Bcl-2 inhibitor

      Noha I. Ziedan, Rania Hamdy, Alessandra Cavaliere, Malamati Kourti, Filippo Prencipe, Andrea Brancale, Arwyn T. Jones and Andrew D. Westwell

      Version of Record online: 24 FEB 2017 | DOI: 10.1111/cbdd.12936

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      A new series of oxadiazoles were designed to act as Bcl-2 inhibitors. Virtual screening led to the discovery of new hits as Bcl-2 inhibitors. SAR study was further performed leading to discovery of a novel lead. Most active compound has submicromolar growth inhibition IC50 for both MDa-MB-231 and HeLa cancer cell lines, and Bcl-2 inhibition in the low micromolar range as demonstrated by ELISA binding assay.

    2. Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies

      Md Ataul Islam and Tahir S. Pillay

      Version of Record online: 24 FEB 2017 | DOI: 10.1111/cbdd.12949

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      Pharmacophore-based virtual screening was performed on DNA GyrB inhibitors. The best selected pharmacophore model explained that two each of hydrogen bond acceptor and hydrophobicity were critical for inhibition of DNA GyrB. On virtual screening of molecular databases using the pharmacophore model, three molecules were found to be promising as antibacterial agents, which was also confirmed by molecular docking and molecular dynamics studies.


    1. In silico approaches and chemical space of anti-P-type ATPase compounds for discovering new antituberculous drugs

      Paola Santos, Fabian López-Vallejo and Carlos-Y. Soto

      Version of Record online: 24 FEB 2017 | DOI: 10.1111/cbdd.12950

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      In this review, we provide an overview on the different models implemented toward the rational design of new anti-TB drugs, encompassing the biological and structural features of Mycobacterium tuberculosis P-type ATPases as possible therapeutic targets. In addition, the chemical space distribution based on the structure and molecular properties of compounds with anti-TB and anti-P-type ATPase activity was assessed and compared to a natural products library. We consider that this library could assist researchers to identify novel chemical scaffolds with potential antituberculous activity.


    1. Synthesis, QSAR studies, and metabolic stability of novel 2-alkylthio-4-chloro-N-(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)benzenesulfonamide derivatives as potential anticancer and apoptosis-inducing agents

      Beata Żołnowska, Jarosław Sławiński, Aneta Pogorzelska, Krzysztof Szafrański, Anna Kawiak, Grzegorz Stasiłojć, Mariusz Belka, Joanna Zielińska and Tomasz Bączek

      Version of Record online: 24 FEB 2017 | DOI: 10.1111/cbdd.12955

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      • New N-(5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)benzenesulfonamides was synthesized
      • The cytotoxic activity toward MCF-7, HeLa, HCT-116 was investigated
      • The 5-oxo-1,2,4-trizines exhibited apoptosis-inducing activity in the HeLa cells
      • The quantitative structure-activity relationship of cytotoxic activity was found
      • Metabolic stability was studied using pooled human liver microsomes and NADPH

    1. Design, synthesis and cytotoxic evaluation of nitric oxide-releasing derivatives of isosteviol

      Yan Liu, Tingting Wang, Yong Ling, Na Bao, Wei Shi, Li Chen and Jianbo Sun

      Version of Record online: 22 FEB 2017 | DOI: 10.1111/cbdd.12956

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      Four series of different types of NO donor-isosteviol derivatives were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control.


    1. Synthesis of primaquine glyco-conjugates as potential tissue schizontocidal antimalarial agents

      Chandra S. Azad, Mridula Saxena, Arif J. Siddiqui, Jyoti Bhardwaj, Sunil K. Puri, Guru P. Dutta, Nitya Anand and Anil K. Saxena

      Version of Record online: 22 FEB 2017 | DOI: 10.1111/cbdd.12944

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      The three compounds viz glucoside (15a), galactoside (15b), and mannoside (15c) with high activity were tested and most active compound 15b showed twofold activity than the standard drug Primaquine diphosphate.

    2. Structural improvement of new thiazolidinones compounds with antinociceptive activity in experimental chemotherapy-induced painful neuropathy

      Diogo Rodrigo Magalhaes Moreira, Dourivaldo Silva Santos, Renan Fernandes do Espírito Santo, Flávia Evangelista dos Santos, Gevanio Bezerra de Oliveira Filho, Ana Cristina Lima Leite, Milena Botelho Pereira Soares and Cristiane Flora Villarreal

      Version of Record online: 22 FEB 2017 | DOI: 10.1111/cbdd.12951

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      Chemotherapy-induced neuropathy is a refractory pain condition resulting from chemotherapy for cancers. In the present study, we describe the structural design, synthesis, chemical and pharmacological characterization of thiazolidinones with antinociceptive effects in a mice model of oxaliplatin-induced neuropathic pain. Thiazolidinones displayed dose-dependent and potent antinociceptive effects, possibly mediated by agonistic properties in PPAR. The structural design of thiazolidinones is an efficient strategy to optimize its pharmacological properties, aiming the control of the refractory neuropathic pain.

    3. Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents

      Amol D. Sonawane, Navnath D. Rode, Laxman Nawale, Rohini R. Joshi, Ramesh A. Joshi, Anjali P. Likhite and Dhiman Sarkar

      Version of Record online: 16 FEB 2017 | DOI: 10.1111/cbdd.12939

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      A series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra. Triazole thiones showed high antitubercular activity against the dormant stage of M. tuberculosis H37Ra. These compounds were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 µg/ml against THP-1, A549, and PANC-1 human cancer cell lines.

    4. 1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H3R/H4R

      Michelle Fidelis Corrêa, Marina Themoteo Varela, Aleksandro Martins Balbino, Ana Claudia Torrecilhas, Richardt Gama Landgraf, Lanfranco Ranieri Paolo Troncone and João Paulo dos Santos Fernandes

      Version of Record online: 16 FEB 2017 | DOI: 10.1111/cbdd.12947

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      Histamine H3R and H4R receptors have been explored as targets for drug discovery. We present herein four non-cytotoxic compounds with moderate affinity for these targets. The compound LINS01005 has shown promising anti-inflammatory activity in murine asthma model.

    5. Physicochemical and biological evaluation of a cinnamamide derivative R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608) for nervous system disorders

      Agnieszka Gunia-Krzyżak, Ewa Żesławska, Florence M. Bareyre, Wojciech Nitek, Anna M. Waszkielewicz and Henryk Marona

      Version of Record online: 16 FEB 2017 | DOI: 10.1111/cbdd.12943

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      R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608), a cinnamamide derivative, with confirmed structure and purity was tested in mice and rats. The compound is a potent anticonvulsant and antiepileptogenic agent. In vivo pharmacological profile of KM-608 corresponds with the activity of valproic acid.

    6. Synthesis, molecular docking and biological evaluation of 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as novel potential tubulin assembling inhibitors

      Yan-Ting Wang, Xun-Chao Cai, Tian-Qi Shi, Ya-Liang Zhang, Zhong-Chang Wang, Chang-Hong Liu and Hai-Liang Zhu

      Version of Record online: 15 FEB 2017 | DOI: 10.1111/cbdd.12932

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      Crystal structure diagram of compound 15. 3D diagram of the interaction between compound 33 and the colchicine-binding site. Compounds of novel 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives containing different substituent groups were designed, synthesized and evaluated for their inhibitory activity against tubulin polymerization and cancer cell growth. Docking simulation and the QSAR study were conducted.

    7. Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex

      Sonja Misirlić Denčić, Jelena Poljarević, Andjelka M. Isakovic, Ivanka Marković, Tibor J. Sabo and Sanja Grgurić-Šipka

      Version of Record online: 14 FEB 2017 | DOI: 10.1111/cbdd.12945

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      This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido complexes with edda type of ligands. Their cytotoxic action, investigated in four human tumor cell lines, showed that novel Pt(II) complexes exhibited comparable or better antitumor action in comparison with cisplatin, precursor ligands, and corresponding Pt(IV) complex.

    8. In silico design and bioevaluation of selective benzotriazepine BRD4 inhibitors with potent antiosteoclastogenic activity

      Vishwa Deepak, Binglin Wang, Dwayne Koot, Abe Kasonga, Xiao Xing Stander, Magdalena Coetzee and Andre Stander

      Version of Record online: 11 FEB 2017 | DOI: 10.1111/cbdd.12930

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      Benzotriazepine bromodomain 4 inhibitors capable of inhibiting osteoclast differentiation without cytotoxic effects on murine RAW264.7 osteoclast progenitors, as well as human CD14+ monocytes, were in silico designed and synthesized. This study demonstrates that in silico docking and molecular dynamics simulations are useful to identify BRD inhibitors with a particular selectivity profile. Furthermore, the compounds identified in this study have remarkable antiosteoclastogenic potential and warrant further studies for drug development against bone loss diseases characterized by excessive osteoclast activity.

    9. Identification and characterization of novel host defense peptides from the skin secretion of the fungoid frog, Hydrophylax bahuvistara (Anura: Ranidae)

      Thundi Parambil Vasanth Kumar Vineeth Kumar, Radhamony Asha, Gopal Shyla and Sanil George

      Version of Record online: 11 FEB 2017 | DOI: 10.1111/cbdd.12937

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      Two novel peptides (brevinin1 HYba1 and brevinin1 HYba2) were identified from the skin secretion of the frog Hydrophylax bahuvistara. Amidation proved to be a favorable modification, which enhanced the biological activity of the brevinin1 peptides without affecting its low hemolytic property. These peptides also showed very high cytotoxicity toward Hep 3B cancer cell lines.

    10. Antilipolytic effects of 1,8-naphthyridine derivatives β-adrenoceptor antagonists in rat white adipocytes

      Jalal A. Aljamal and Muwaffag Badawneh

      Version of Record online: 11 FEB 2017 | DOI: 10.1111/cbdd.12933

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      A series of novel 1,8-naphthyridine derivatives variously modified were synthesized and their β-AR blocking activities were determined. Preliminary evidence suggests that the inhibitory effects of the newly synthesized 1,8-naphthyridine analogues 3 and 10 on either alprenolol or isoprenaline-induced lipolysis in rat fat cells may result from inhibition of the low-affinity β3-adrenoceptor.

    11. Biofocussed chemoprospecting: An efficient approach for drug discovery

      Balmukund Sureshkumar Thakkar, Marte Albrigtsen, John Sigurd Svendsen, Jeanette H. Andersen and Richard Alan Engh

      Version of Record online: 7 FEB 2017 | DOI: 10.1111/cbdd.12934

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      “Biofocussed chemoprospecting” represents a hybrid of bioprospecting and a scaffold-based approach and includes property filtering to optimize qualities such as diversity, drug likeness, ease of synthesis, low cost and “bio likeness.” To demonstrate this approach, we generated two dipeptide-based libraries, first as large virtual libraries, followed by focussed synthesis. The resultant libraries demonstrated a hit rate comparable to target-based approaches, with additional potential to identify new targets and mechanisms.

    12. Synthesis and investigation of anticancer potential of radiolabeled naphthalene monoimide bearing imidazolium salt

      Fatma Yurt Lambrecht, Kasim Ocakoglu, Suleyman Gokhan Colak, Onur Alp Ersoz and Ozge Er

      Version of Record online: 7 FEB 2017 | DOI: 10.1111/cbdd.12935

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      In this study, the antitumor potential of 131I-NMI in HEK-293, CaCo-2, MCF-7, and PC-3 cell lines were evaluated with the intracellular uptake studies. 131I-labeled NMI showed significant uptake efficiency in MCF-7 and PC-3 cell lines. Further investigation is also necessary in tumor-bearing animals to clarify the potential of radiolabeled NMI for breast and prostate tumor imaging.

    13. New 3-alkylpyridine marine alkaloid analogues as promising antitumor agents against the CD44+/high/CD24−/low subset of triple-negative breast cancer cell line

      Aline Brito de Lima, Camila de Souza Barbosa, Alessandra Mirtes Marques Neves Gonçalves, Fabio Vieira dos Santos, Gustavo Henrique Ribeiro Viana, Fernando de Pilla Varotti and Luciana Maria Silva

      Version of Record online: 7 FEB 2017 | DOI: 10.1111/cbdd.12923

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      Triple-negative breast cancer (TNBC) is one of the most aggressive cancers in women. In this study, six synthetic 3-alkylpyridine marine alkaloid analogues were tested for cytotoxic activity against TNBC cell line and tumorspheres derived from BT-549.


    1. Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors

      Mateusz Daśko, Janusz Rachon, Maciej Masłyk, Konrad Kubiński and Sebastian Demkowicz

      Version of Record online: 7 FEB 2017 | DOI: 10.1111/cbdd.12931

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      In this study, we report convenient methods for the synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds exhibiting STS activity. Additionally, their binding modes have been modeled using docking techniques. New tyramine analogs occurred to be potent STS inhibitors and revealed promising activity in vitro.


    1. Molecular dynamics simulation on the inhibition mechanism of peptide-based inhibitor of islet amyloid polypeptide (IAPP) to islet amyloid polypeptide (IAPP22–28) oligomers

      Shuangyan Zhou, Qianqian Wang, Mengdan Ren, Ai Zhang, Huanxiang Liu and Xiaojun Yao

      Version of Record online: 7 FEB 2017 | DOI: 10.1111/cbdd.12924

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      Molecular dynamics (MD) simulations were performed for NFGAIL oligomers, with the outer edge of the β-sheet in the state of N-methylation at position Gly24 and Ile26 or not, to explore the inhibition mechanism of peptide inhibitor under template induction process.

    2. Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities

      Heba A. Abd El Razik, Mohamad Mroueh, Wissam H. Faour, Wassim N. Shebaby, Costantine F. Daher, Hayam M. A. Ashour and Hanan M. Ragab

      Version of Record online: 6 FEB 2017 | DOI: 10.1111/cbdd.12929

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      Compounds showing dual anticancer/anti-inflammatory activity are of increasing interest for the treatment of cancer due to the implication of inflammatory mechanisms in most malignancies. This spurred the synthesis of compounds containing a purine character (a scaffold for anticancer drugs) together with a pyrazole moiety (a scaffold for anti-inflammatory agents). Among these compounds, 10b was the most active against all used cell lines.

    3. Simplified, serine-rich theta-defensin analogues as antitumour peptides

      Paulina Strzelecka, Dominika Czaplinska, Rafal Sadej, Anna Wardowska, Michal Pikula and Adam Lesner

      Version of Record online: 6 FEB 2017 | DOI: 10.1111/cbdd.12927

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      θ-defensins are cyclic, host defence peptides with strong antimicrobial activity. In the current study, we aimed to define anticancer potential of θ-defensin analogues. Their serine-containing derivatives were more cytotoxic against breast cancer cells (SKBR3, MDA-MB-231) than against mammary epithelial cells (HB2). Analogues also enhanced the effect of cisplatin and doxorubicin hydrochloride on triple-negative breast cancer cell line (MDA-MB-231).


    1. Emerging biopharmaceuticals from bioactive peptides derived from marine organisms

      Komal Anjum, Syed Qamar Abbas, Najeeb Akhter, Bibi Ibtesam Shagufta, Sayed Asmat Ali Shah and Syed Shams ul Hassan

      Version of Record online: 6 FEB 2017 | DOI: 10.1111/cbdd.12925

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      Marine peptides are a drug treasure house. Marine peptides are one of the major needs for pharmaceutical and nutraceuticals. The mode of action of every biomolecule is one of the basic tools to be known for transformation of bioactive compound into medicines.


    1. Design, synthesis and pharmacophoric model building of new 3-alkoxymethyl/3-phenyl indole-2-carboxamides with potential antiproliferative activity

      Mostafa H. Abdelrahman, Ahmed S. Aboraia, Bahaa G. M. Youssif and Bakheet E. M. Elsadek

      Version of Record online: 31 JAN 2017 | DOI: 10.1111/cbdd.12928

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      1. Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and biologically evaluated for anticancer potential.

      2. Pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through addition of acceptor or donating groups to the already-present indole nucleus.

    2. Structure-based approaches for the design of benzimidazole-2-carbamate derivatives as tubulin polymerization inhibitors

      Rodrigo Aguayo-Ortiz, Lucia Cano-González, Rafael Castillo, Alicia Hernández-Campos and Laura Dominguez

      Version of Record online: 30 JAN 2017 | DOI: 10.1111/cbdd.12926

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      β-Tubulin isotypes are attractive therapeutic targets for the design of specific anticancer treatments. Herein, we carried out docking and molecular dynamics simulations to determine the binding mode of a series of benzimidazole-2-carbamete derivatives in the βI-, βIII-, and βVI-tubulin isotypes. Finally, we propose novel approaches in the design of BzCs as microtubule polymerization inhibitors with a potential higher affinity to βI and βIII isotypes compared to that to the βVI isotype.


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