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  Subjects -> CHEMISTRY (Total: 823 journals)
    - ANALYTICAL CHEMISTRY (49 journals)
    - CHEMISTRY (570 journals)
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CHEMISTRY (570 journals)                  1 2 3 4 5 6 | Last

2D Materials     Hybrid Journal   (Followers: 4)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 31)
ACS Catalysis     Full-text available via subscription   (Followers: 25)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 13)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 8)
ACS Macro Letters     Full-text available via subscription   (Followers: 20)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 25)
ACS Nano     Full-text available via subscription   (Followers: 361)
ACS Photonics     Full-text available via subscription   (Followers: 6)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 11)
Acta Chemica Iasi     Open Access  
Acta Chimica Sinica     Full-text available via subscription  
Acta Chimica Slovaca     Open Access   (Followers: 6)
Acta Chromatographica     Full-text available via subscription   (Followers: 10)
Acta Facultatis Medicae Naissensis     Open Access   (Followers: 1)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 4)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 5)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 10)
Advanced Functional Materials     Hybrid Journal   (Followers: 39)
Advances in Chemical Engineering and Science     Open Access   (Followers: 23)
Advances in Chemical Science     Open Access   (Followers: 9)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 15)
Advances in Drug Research     Full-text available via subscription   (Followers: 17)
Advances in Enzyme Research     Open Access  
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 13)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 16)
Advances in Nanoparticles     Open Access   (Followers: 12)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Polymer Science     Hybrid Journal   (Followers: 39)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 10)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 4)
African Journal of Chemical Education     Open Access   (Followers: 1)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 5)
Afrique Science : Revue Internationale des Sciences et Technologie     Open Access   (Followers: 1)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 1)
Alchemy     Open Access   (Followers: 3)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 5)
AMB Express     Open Access  
Ambix     Hybrid Journal   (Followers: 2)
American Journal of Applied Sciences     Open Access   (Followers: 31)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 216)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 12)
American Journal of Chemistry     Open Access   (Followers: 18)
American Journal of Plant Physiology     Open Access   (Followers: 10)
American Mineralogist     Full-text available via subscription   (Followers: 7)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 18)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 275)
Annales UMCS, Chemia     Open Access   (Followers: 2)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 1)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 2)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 10)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 11)
Anti-Infective Agents     Hybrid Journal   (Followers: 1)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 4)
Applied Spectroscopy     Full-text available via subscription   (Followers: 12)
Applied Surface Science     Hybrid Journal   (Followers: 21)
Arabian Journal of Chemistry     Full-text available via subscription   (Followers: 6)
ARKIVOC     Open Access   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 4)
Autophagy     Full-text available via subscription   (Followers: 1)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 7)
Biochemistry     Full-text available via subscription   (Followers: 274)
Biochemistry Insights     Open Access   (Followers: 4)
Biochemistry Research International     Open Access   (Followers: 4)
BioChip Journal     Hybrid Journal   (Followers: 1)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 4)
Bioinspired Materials     Open Access  
Biointerface Research in Applied Chemistry     Open Access   (Followers: 1)
Biointerphases     Open Access  
Biomacromolecules     Full-text available via subscription   (Followers: 17)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 5)
Biomedical Chromatography     Hybrid Journal   (Followers: 7)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 2)
BioNanoScience     Partially Free   (Followers: 4)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 30)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 24)
Bioorganic Chemistry     Hybrid Journal   (Followers: 5)
Biopolymers     Hybrid Journal   (Followers: 14)
Biosensors     Open Access   (Followers: 3)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 13)
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 3)
Canadian Journal of Chemistry     Full-text available via subscription   (Followers: 6)
Canadian Mineralogist     Full-text available via subscription   (Followers: 1)
Carbohydrate Research     Hybrid Journal   (Followers: 11)
Carbon     Hybrid Journal   (Followers: 55)
Catalysis for Sustainable Energy     Open Access   (Followers: 2)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 6)
Catalysis Science and Technology     Free   (Followers: 4)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 4)

        1 2 3 4 5 6 | Last

Journal Cover   Bioorganic & Medicinal Chemistry
  [32 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0968-0896
   Published by Elsevier Homepage  [2588 journals]
  • Native chemical ligation between Asparagine and Valine: Application and
           limitations for the synthesis of tri-phosphorylated C-terminal tau
    • Abstract: Publication date: Available online 17 March 2015
      Source:Bioorganic & Medicinal Chemistry
      Author(s): Oliver Reimann , Maria Glanz , Christian P.R. Hackenberger
      We present the successful native chemical ligation (NCL) at an Asn-Val site employing β-mercaptovaline and subsequent desulfurization in the synthesis of native phosphorylated C-terminal tau, relevant for Alzheimer’s disease related research. Despite recent progress in the field of NCL we illustrate limitations of this ligation site that stem from thioester hydrolysis and predominantly aspartimide formation. We systematically investigated the influence of pH, temperature, peptide concentration and thiol additives on the outcome of this ligation and identified conditions under which the ligation can be driven toward complete conversion, which required the deployment of a high surplus of thioester. Application of the optimized conditions allowed us to gain access to challenging tri-phosphorylated C-terminal tau peptide in practical yields.
      Graphical abstract image

      PubDate: 2015-03-19T03:42:25Z
       
  • Design, Synthesis and Biological Evaluation of Novel Homocamptothecin
           Analogues as Potent Antitumor Agents
    • Abstract: Publication date: Available online 18 March 2015
      Source:Bioorganic & Medicinal Chemistry
      Author(s): Lei Wang , Shao Xie , Longjun Ma , Yi Chen , Wei Lu
      Fifteen novel homocamptothecin derivatives with α-OMe substituted E-rings were designed and synthesized. All of the derivatives exhibited similar or superior cytotoxicities compared with that of SN-38, and they inhibited Topo I activity in a cell-free assay in a manner similar to that of SN-38, confirming that they represent a new class of Topo I inhibitors. Notably, the water soluble compound 36o (1.2 mg/mL) exhibited increased lactone stability, and at 0.5 mg/kg and 3.0 mg/kg, it demonstrated significant antitumor activity in mice bearing a xenograft model using human colon cancer cell line HT-29. On the basis of these positive results, further development of 36o-related compounds as potential anticancer clinical trial candidates is definitely warranted.
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      PubDate: 2015-03-19T03:42:25Z
       
  • Identification of novel class of falcipain-2 inhibitors as potential
           antimalarial agents
    • Abstract: Publication date: Available online 18 March 2015
      Source:Bioorganic & Medicinal Chemistry
      Author(s): Sai Kumar Chakka , Mohammad Kalamuddin , Srividhya Sundararaman , Lianhu Wei , Sourabh Mundra , Radhakrishnan Mahesh , Pawan Malhotra , Asif Mohmmed , Lakshmi P. Kotra
      Falcipain-2 is a papain family cysteine protease and an emerging antimalarial drug target. A pseudo-tripeptide scaffold I was designed using in silico screening tools and the three dimensional structures of falcipain-2, falcipain-3, and papain. This scaffold was investigated at four positions, T1, T2, T3, and T3′, with various targeted substitutions to understand the structure-activity relationships. Inhibitor synthesis was accomplished by first obtaining the appropriate dipeptide precursors with common structural components. The pyrrolidine moiety introduced interesting rotamers in a number of synthesized molecules, which was confirmed using high-temperature 1H NMR spectroscopy. Among the synthesized compounds, 61, 62, and 66 inhibited falcipain-2 activity with inhibition constants (K i) of 1.8 ± 1.1, 0.2 ± 0.1 and 7.0 ± 2.3 μM, respectively. A group of molecules with a pyrrolidine moiety at the T2 position (68, 70, 71, 72, and 73) also potently inhibited falcipain-2 activity (K i = 0.4 ± 0.1, 2.5 ± 0.5, 3.3 ± 1.1, 7.5 ± 1.9, and 4.6 ± 0.7 μM, respectively). Overall, compound 74 exhibited potent anti-parasitic activity (IC50 = 0.9 ± 0.1 μM), corresponding with its inhibitory activity against falcipain-2, with a K i of 1.1 ± 0.1 μM. Compounds 62 and 67 inhibited the growth of the drug resistant parasite Dd2 with better efficacy, and compound 74 exhibited a 7- to 12-fold higher potency against Dd2 and MCamp isolates, than the laboratory strain (3D7). These data suggest that this novel series of compounds should be further investigated as potential antimalarial agents.
      Graphical abstract image

      PubDate: 2015-03-19T03:42:25Z
       
  • Rational design of allosteric-inhibition sites in classical protein
           tyrosine phosphatases
    • Abstract: Publication date: Available online 17 March 2015
      Source:Bioorganic & Medicinal Chemistry
      Author(s): Cynthia M. Chio , Xiaoling Yu , Anthony C. Bishop
      Protein tyrosine phosphatases (PTPs), which catalyze the dephosphorylation of phosphotyrosine in protein substrates, are critical regulators of metazoan cell signaling and have emerged as potential drug targets for a range of human diseases. Strategies for chemically targeting the function of individual PTPs selectively could serve to elucidate the signaling roles of these enzymes and would potentially expedite validation of the therapeutic promise of PTP inhibitors. Here we report a novel strategy for the design of non-natural allosteric-inhibition sites in PTPs; these sites, which can be introduced into target PTPs through protein engineering, serve to sensitize target PTPs to potent and selective inhibition by a biarsenical small molecule. Building on the recent discovery of a naturally occurring cryptic allosteric site in wild-type Src-homology-2 domain containing PTP (Shp2) that can be targeted by biarsenical compounds, we hypothesized that Shp2’s unusual sensitivity to biarsenicals could be strengthened through rational design and that the Shp2-specific site could serve as a blueprint for the introduction of non-natural inhibitor sensitivity in other PTPs. Indeed, we show here that the strategic introduction of a cysteine residue at a position removed from the Shp2 active site can serve to increase the potency and selectivity of the interaction between Shp2’s allosteric site and the biarsenical inhibitor. Moreover, we find that “Shp2-like” allosteric sites can be installed de novo in PTP enzymes that do not possess naturally occurring sensitivity to biarsenical compounds. Using primary-sequence alignments to guide our enzyme engineering, we have successfully introduced allosteric-inhibition sites in four classical PTPs—PTP1B, PTPH-1, FAP-1, and HePTP—from four different PTP subfamilies, suggesting that our sensitization approach can likely be applied widely across the classical PTP family to generate biarsenical-responsive PTPs.
      Graphical abstract image

      PubDate: 2015-03-19T03:42:25Z
       
  • Novel curcumin analogs to overcome EGFR–TKI lung adenocarcinoma drug
           resistance and reduce EGFR–TKI-induced GI adverse effects
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Koji Wada , Jen-Yi Lee , Hsin-Yi Hung , Qian Shi , Li Lin , Yu Zhao , Masuo Goto , Pan-Chyr Yang , Sheng-Chu Kuo , Hui-Wen Chen , Kuo-Hsiung Lee
      Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression as well as phosphorylation in two gefitinib-resistant lung adenocarcinoma cell lines, CL1-5 (EGFRwt) and H1975 (EGFRL858R+T790M). Based on the identified structure–activity relationships, methoxy substitution at C-3′, C-4′, or both positions favored inhibitory activity (compounds 1, 2, 5, 8–15, 17, 36), while compounds with more polar substituents were generally less active in both cell lines. Compound 36 with a fluorine substituent at C-6′ and its protonated counterpart 2 did not lose activity, suggesting halogen tolerance. In addition, a conjugated linker was essential for activity. Among all evaluated curcumin derivatives, compound 2 showed the best inhibitory effects on both wild-type and mutant EGFR by efficiently inducing gefitinib-insensitive EGFR degradation. Compound 23 also reduced gefitinib-induced gastrointestinal damage in the non-transformed intestinal epithelial cell line IEC-18.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • 18F-AmBF3-MJ9: A novel radiofluorinated bombesin derivative for prostate
           cancer imaging
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Maral Pourghiasian , Zhibo Liu , Jinhe Pan , Zhengxing Zhang , Nadine Colpo , Kuo-Shyan Lin , David M. Perrin , François Bénard
      A novel radiofluorinated derivative of bombesin, 18F-AmBF3-MJ9, was synthesized and evaluated for its potential to image prostate cancer by targeting the gastrin releasing peptide receptor (GRPR). AmBF3-MJ9 was prepared from an ammoniomethyl-trifluoroborate (AmBF3) conjugated alkyne 2 and azidoacetyl-MJ9 via a copper-catalyzed click reaction, and had good binding affinity for GRPR (K i =0.5±0.1nM). The 18F-labeling was performed via a facile one-step 18F–19F isotope exchange reaction, and 18F-AmBF3-MJ9 was obtained in 23±5% (n =3) radiochemical yield in 25min with >99% radiochemical purity and 100±32GBq/μmol specific activity. 18F-AmBF3-MJ9 was stable in mouse plasma, and was partially (22–30%) internalized after binding to GRPR. Positron emission tomography (PET) imaging and biodistribution studies in mice showed fast renal excretion and good uptake of 18F-AmBF3-MJ9 by GRPR-expressing pancreas and PC-3 prostate cancer xenografts. Tumor uptake was 1.37±0.25%ID/g at 1h, and 2.20±0.13%ID/g at 2h post-injection (p.i.) with low background uptake and excellent tumor visualization (tumor-to-muscle ratios of 75.4±5.5). These data suggest that 18F-AmBF3-MJ9 is a promising PET tracer for imaging GRPR-expressing prostate cancers.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Identification of Bacillus anthracis PurE inhibitors with antimicrobial
           activity
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Anna Kim , Nina M. Wolf , Tian Zhu , Michael E. Johnson , Jiangping Deng , James L. Cook , Leslie W.-M. Fung
      N5-carboxy-amino-imidazole ribonucleotide (N5-CAIR) mutase (PurE), a bacterial enzyme in the de novo purine biosynthetic pathway, has been suggested to be a target for antimicrobial agent development. We have optimized a thermal shift method for high-throughput screening of compounds binding to Bacillus anthracis PurE. We used a low ionic strength buffer condition to accentuate the thermal shift stabilization induced by compound binding to Bacillus anthracis PurE. The compounds identified were then subjected to computational docking to the active site to further select compounds likely to be inhibitors. A UV-based enzymatic activity assay was then used to select inhibitory compounds. Minimum inhibitory concentration (MIC) values were subsequently obtained for the inhibitory compounds against Bacillus anthracis (ΔANR strain), Escherichia coli (BW25113 strain, wild-type and ΔTolC), Francisella tularensis, Staphylococcus aureus (both methicillin susceptible and methicillin-resistant strains) and Yersinia pestis. Several compounds exhibited excellent (0.05–0.15μg/mL) MIC values against Bacillus anthracis. A common core structure was identified for the compounds exhibiting low MIC values. The difference in concentrations for inhibition and MIC suggest that another enzyme(s) is also targeted by the compounds that we identified.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis and biological evaluation of fluconazole analogs with
           triazole-modified scaffold as potent antifungal agents
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Seyedeh Mahdieh Hashemi , Hamid Badali , Hamid Irannejad , Mohammad Shokrzadeh , Saeed Emami
      In order to find new azole antifungals, we have recently designed a series of triazole alcohols in which one of the 1,2,4-triazol-1-yl group in fluconazole structure has been replaced with 4-amino-5-aryl-3-mercapto-1,2,4-triazole motif. In this paper, we focused on the structural refinement of the primary lead, by removing the amino group from the structure to achieve 5-aryl-3-mercapto-1,2,4-triazole derivatives 10a–i and 11a–i. The in vitro antifungal susceptibility testing of title compounds demonstrated that most compounds had potent inhibitory activity against Candida species. Among them, 5-(2,4-dichlorophenyl)triazole analogs 10h and 11h with MIC values of <0.01 to 0.5μg/mL were 4–256 times more potent than fluconazole against Candida species.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • The short way to chiral compounds with hexahydrofluoreno[9,1-bc]furan
           framework: Synthesis and cytotoxic activity
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Svetlana Yu. Kurbakova , Irina V. Il‘ina , Oksana S. Mikhalchenko , Mikhail A. Pokrovsky , Dina V. Korchagina , Konstantin P. Volcho , Andrey G. Pokrovsky , Nariman F. Salakhutdinov
      A simple and efficient method for synthesizing chiral heterocyclic compounds with the hexahydrofluoreno[9,1-bc]furan framework via interaction between trans-4-hydroxymethyl-2-carene and aromatic aldehydes containing methoxy and hydroxyl moieties in the presence of montmorillonite clay was found. One of the synthesized compounds exhibited a high cytotoxic activity against lymphoblastoid cell line MT-4 (CTD50 0.9μM), which was higher than that of the comparative drug Doxorubicin. Death of cancer cells in this case substantially occurs via induction of apoptosis.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis and evaluation of tetrahydroindazole derivatives as sigma-2
           receptor ligands
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Zong-Wen Wu , Shu-Yong Song , Li Li , He-Lin Lu , Brian Lieberman , Yun-Sheng Huang , Robert H. Mach
      A series of tetrahydroindazole derivatives were synthesized and evaluated for their affinities for both sigma-1 and sigma-2 receptors. These compounds are hybrid structures of a tetrahydroindazole substituted benzamide and a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety or a 9-azabicyclo[3.3.1]nonan-3-yl-amine moiety. These newly synthesized hybrid analogs showed various affinities for sigma-2 receptor without any significant affinities for sigma-1 receptor. In particular, compounds 12, 15b, 15c, and 15d, demonstrated moderate affinity and excellent selectivity for sigma-2 receptor. It is interesting to note that 3–5 carbon units between the tetrahydroindazole substituted benzamide and the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety are appropriate for sigma-2 receptor binding. No substitution on the 9-aza nitrogen is proper for sigma-2 affinity in the 2-(9-azabicyclo[3.3.1]nonan-3-yl-amino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide analogs.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Pheophorbide-a conjugates with cancer-targeting moieties for targeted
           photodynamic cancer therapy
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Hyun You , Hyo-Eun Yoon , Pyeong-Hwa Jeong , Hyojin Ko , Jung-Hoon Yoon , Yong-Chul Kim
      Pheophorbide-a, a non-selective photosensitizer, was conjugated with cancer-targeting moieties, such as folic acid, the CRGDLASLC peptide, the cRGDfK peptide and leuprorelin, for the purpose of targeted photodynamic cancer therapy. The cellular uptake of pheophorbide-a conjugates in cancer cells overexpressing the corresponding receptors of the targeting moieties was largely enhanced compared with that in the receptor-negative cells. In the study of in vitro photodynamic activity and selectivity of pheophorbide-a conjugates in the receptor-positive and receptor-negative cells, a pheophorbide-a conjugate, (14) with an αvβ6 ligand (CRGDLASLC) exhibited the highest selectivity in the positive FaDu cells. Targeted PDT with 14 induced cell death through apoptosis and morphological apoptosis-like characteristics. These results suggest that pheophorbide-a conjugate 14 could be utilized in selective photodynamic therapy for oral cancers primarily expressing the αvβ6 receptor.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Identification of anti-HIV agents with a novel
           benzo[4,5]isothiazolo[2,3-a]pyrimidine scaffold
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Shiho Okazaki , Tsukasa Mizuhara , Kazuya Shimura , Hiroto Murayama , Hiroaki Ohno , Shinya Oishi , Masao Matsuoka , Nobutaka Fujii
      3,4-Dihydro-2H-benzo[4,5]isothiazolo[2,3-a]pyrimidine is a newly identified antiviral agent against human immunodeficiency virus type 1 (HIV-1) infection, derived from 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182). The introduction of the hydrophobic 8-aryl substituent on the benzene substructure improved its anti-HIV activity, resulting in the identification of 6-fold more potent analogs. In addition, it was demonstrated that these isothiazolopyrimidine derivatives exert anti-HIV effects at an early stage of viral infection.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis and antitumor activity of novel per-butyrylated glycosides of
           podophyllotoxin and its derivatives
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Cheng-Ting Zi , Dan Yang , Fa-Wu Dong , Gen-Tao Li , Yan Li , Zhong-Tao Ding , Jun Zhou , Zi-Hua Jiang , Jiang-Miao Hu
      A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d-galactopyranoside 8b, epipodophyllotoxin α-d-arabinopyranoside 8e, and podophyllotoxin β-d-glucopyranoside 11a show the highest potency of anticancer activity with their IC50 values ranging from 0.14 to 1.69μM. Structure activity relationship analysis indicates that the type of glycosidic linkage, the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4′-position (OH vs OCH3) can all have significant effect on the potency of their anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin, suggesting their potential as anticancer agents for further development.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis of 6-aryl-substituted sulfocoumarins and investigation of their
           carbonic anhydrase inhibitory action
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Aiga Grandane , Muhammet Tanc , Raivis Žalubovskis , Claudiu T. Supuran
      A series of 6-aryl-substituted 1,2-benzoxathiine 2,2-dioxides was obtained by reacting 6-iodo-sulfocoumarin with arylboronic acids in Suzuki cross-coupling conditions. The new sulfocoumarins incorporating various substituted phenyl moieties in position 6 of the heterocyclic ring were investigated for the inhibition of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms with medicinal chemistry applications, the cytosolic hCA I and II, and the transmembrane, tumor-associated hCA IX and XII. The aryl-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (K Is>10μM) but showed effective inhibition against the two transmembrane CAs, with K Is ranging from 9.0 to 95.3nM against hCA IX, and between 3.5 and 14.2nM against hCA XII. As hCA IX and XII are validated anti-tumor targets, such sulfocoumarin, isoform-selective inhibitors may be useful for identifying suitable drug candidates for further clinical trials of this class of pharmacologic agents.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Aminobenzoic acid incorporated octapeptides for cation transport
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Bahiru P. Benke , Nandita Madhavan
      Robust oligopeptides that mimic natural ion channels are attractive for use as molecular switches or model systems to study ion transport. Herein, we report octapeptides derived from aminobenzoic acid and l/d amino acids. Two of the alanine containing peptides were found to be most active and the peptide containing p-aminobenzoic acid was found to be most active (2.4 times its m-analog). Experimental studies indicate the peptides do not transport halides and transport alkali metal ions.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • New approaches to the synthesis of sildenafil analogues and their enzyme
           inhibitory activity
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Mariusz Mojzych , Zbigniew Karczmarzyk , Waldemar Wysocki , Mariangela Ceruso , Claudiu T. Supuran , Vladimir Kryštof , Zofia Urbańczyk-Lipkowska , Przemysław Kalicki
      In the search for new biologically active chemotypes, several sildenafil analogs were prepared and characterized. The presence of the pyrazolo[4,3-e][1,2,4]triazine core is thought to be of interest for the enzyme inhibitory activity of these compounds. The designed derivatives incorporating the sildenafil scaffold were assayed as carbonic anhydrase inhibitors, and for their cytotoxic activity against MCF-7 and K562 cell lines. The X-ray analysis of one of these model compounds was performed and its crystal structure is described/compared to that of sildenafil.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Development of 2-amino-5-phenylthiophene-3-carboxamide derivatives as
           novel inhibitors of Mycobacterium tuberculosis DNA GyrB domain
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Shalini Saxena , Ganesh Samala , Janupally Renuka , Jonnalagadda Padma Sridevi , Perumal Yogeeswari , Dharmarajan Sriram
      DNA gyrase is the only type II topoisomerase in Mycobacterium tuberculosis (Mtb), unlike other bacteria and its absence in human being makes it a clinically validated target for developing anti-tubercular leads against Mtb. In the present study, our effort was to optimize and synthesize a series of compounds by a combination of molecular docking, and synthetic chemistry approach for better activity. A series of twenty eight substituted 2-amino-5-phenylthiophene-3-carboxamide derivatives were designed based on our earlier reported Mtb GyrB inhibitor lead. Hit expansion of the previously identified lead by chemical synthesis led to improved inhibitor with an IC50 value of 0.86±0.81μM against Mtb DNA gyrase supercoiling and Mycobacterium smegmatis GyrB IC50 of 1.35±0.58μM. Further a biophysical investigation using differential scanning fluorimetry experiments re-ascertained the affinity of these molecules towards the GyrB domain.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis and antifungal activity of
           5-iodo-1,4-disubstituted-1,2,3-triazole derivatives as pyruvate
           dehydrogenase complex E1 inhibitors
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Jun-Bo He , Hai-Feng He , Lu-Lu Zhao , Li Zhang , Ge-Yun You , Ling-Ling Feng , Jian Wan , Hong-Wu He
      To identify new antifungal lead compound based on inhibitors of pyruvate dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1 inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc-E1 inhibition indicated all the compounds exhibited significant inhibition against E. coli PDHc-E1 (IC50 <21μM), special compound 3g showed the most potent inhibitory activity (IC50 =4.21±0.11μM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5μg/mL. Especially compound 3n (EC50 =5.4μg/mL; EC90 =21.1μg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50 =29.6μg/mL; EC90 =113.4μg/mL). Therefore, in this study, compound 3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Corrigendum to “VBP15: Preclinical characterization of a novel
           anti-inflammatory delta 9,11 steroid” [Bioorg. Med. Chem. 21 (2013)
           2241–2249]
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Erica K.M. Reeves , Eric P. Hoffman , Kanneboyina Nagaraju , Jesse M. Damsker , John M. McCall



      PubDate: 2015-03-15T03:40:34Z
       
  • Corrigendum to “Structure-guided design and development of novel
           benzimidazole class of compounds targeting DNA gyraseB enzyme of
           Staphylococcus aureus” [Bioorg. Med. Chem. 22 (2014)
           5970–5987]
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Renuka Janupally , Variam Ullas Jeankumar , Karyakulam Andrews Bobesh , Vijay Soni , Parthiban Brindha Devi , Venkat Koushik Pulla , Priyanka Suryadevara , Keerthana Sharma Chennubhotla , Pushkar Kulkarni , Perumal Yogeeswari , Dharmarajan Sriram



      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis and biological activity evaluation of hydrazone derivatives
           based on a Tröger’s base skeleton
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Robert Kaplánek , Martin Havlík , Bohumil Dolenský , Jakub Rak , Petr Džubák , Petr Konečný , Marián Hajdúch , Jarmila Králová , Vladimír Král
      We report the design and synthesis of novel anticancer agents based on bis-hydrazones separated by a rigid Tröger’s base skeleton. This novel approach combines a biologically active moiety (hydrazone) with this scaffold (Tröger’s base) to construct DNA intercalators. Evaluation of the anticancer activity of these agents using seven cancer cell lines and two healthy cell lines found that several derivatives had potent anticancer activity and excellent selectivity indexes toward cancer cells. The antimicrobial activities were tested on a set of thirteen bacterial stains, but the prepared compounds were not active. Complexation studies using biologically important metal ions demonstrated that these compounds are able to bind Cu2+, Fe3+, Co2+, Ni2+ and Zn2+. DNA intercalation studies showed that the compounds themselves do not interact with DNA, but their metallocomplexes do interact, most likely via intercalation into DNA.
      Graphical abstract image

      PubDate: 2015-03-15T03:40:34Z
       
  • Corrigendum to “A dual inhibitor of matrix metalloproteinases and a
           disintegrin and metalloproteinases, [18F]FB-ML5, as a molecular probe for
           non-invasive MMP/ADAM-targeted imaging” [Bioorg. Med. Chem. 23
           (2014) 192–202]
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Nathalie Matusiak , Riccardo Castelli , Adriaan W. Tuin , Herman S. Overkleeft , Rosalina Wisastra , Frank J. Dekker , Laurette M. Prély , Rainer Bischoff , Aren van Waarde , Rudi A.J.O. Dierckx , Philip H. Elsinga



      PubDate: 2015-03-15T03:40:34Z
       
  • Triazole-containing N-acyl homoserine lactones targeting the quorum
           sensing system in Pseudomonas aeruginosa
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Mette R. Hansen , Tim H. Jakobsen , Claus G. Bang , Anders Emil Cohrt , Casper L. Hansen , Janie W. Clausen , Sebastian T. Le Quement , Tim Tolker-Nielsen , Michael Givskov , Thomas E. Nielsen
      In an attempt to devise new antimicrobial treatments for biofilm infections, the bacterial cell–cell communication system termed quorum sensing has emerged as an attractive target. It has proven possible to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify the structural elements important for antagonistic or agonistic activity against the Pseudomonas aeruginosa LasR protein, we report the synthesis and screening of new triazole-containing mimics of natural N-acyl homoserine lactones. A series of azide- and alkyne-containing homoserine lactone building blocks was used to prepare an expanded set of 123 homoserine lactone analogues through a combination of solution- and solid-phase synthesis methods. The resulting compounds were subjected to cell-based quorum sensing screening assays, thereby revealing several bioactive compounds, including 13 compounds with antagonistic activity and 9 compounds with agonistic activity.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Stereoselective synthesis, biological evaluation, and modeling of novel
           bile acid-derived G-protein coupled Bile acid receptor 1 (GP-BAR1, TGR5)
           agonists
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Donna D. Yu , Kyle M. Sousa , Daniell L. Mattern , Jeffrey Wagner , Xianghui Fu , Nagarajan Vaidehi , Barry M. Forman , Wendong Huang
      GP-BAR1 (also known as TGR5), a novel G-protein coupled receptor regulating various non-genomic functions via bile acid signaling, has emerged as a promising target for metabolic disorders, including obesity and type II diabetes. However, given that many bile acids (BAs) are poorly tolerated for systemic therapeutic use, there is significant need to develop GP-BAR1 agonists with improved potency and specificity and there also is significant impetus to develop a stereoselective synthetic methodology for GP-BAR1 agonists. Here, we report the development of highly stereo-controlled strategies to investigate a series of naturally occurring bile acid derivatives with markedly enhanced GP-BAR1 activity. These novel GP-BAR1 agonists are evaluated in vitro using luciferase-based reporter and cAMP assays to elucidate their biological properties. In vivo studies revealed that the GP-BAR1 agonist 23(S)-m-LCA increased intestinal GLP-1 transcripts by 26-fold. Additionally, computational modeling studies of selected ligands that exhibit enhanced potency and specificity for GP-BAR1 provide information on potential binding sites for these ligands in GP-BAR1.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Isoindoline-1,3-dione derivatives targeting cholinesterases: Design,
           synthesis and biological evaluation of potential anti-Alzheimer’s
           agents
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Natalia Guzior , Marek Bajda , Jurand Rakoczy , Boris Brus , Stanislav Gobec , Barbara Malawska
      Alzheimer’s disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer’s disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50 =0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood–brain barrier indicated that the compound 3b would be able to cross the blood–brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer’s agents.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Structure–activity study for (bis)ureidopropyl- and
           (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon
           backbone architectures
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Shannon L. Nowotarski , Boobalan Pachaiyappan , Steven L. Holshouser , Craig J. Kutz , Youxuan Li , Yi Huang , Shiv K. Sharma , Robert A. Casero Jr. , Patrick M. Woster
      Methylation at specific histone lysine residues is a critical post-translational modification that alters chromatin architecture, and dysregulated lysine methylation/demethylation is associated with the silencing of tumor suppressor genes. The enzyme lysine-specific demethylase 1 (LSD1) complexed to specific transcription factors catalyzes the oxidative demethylation of mono- and dimethyllysine 4 of histone H3 (H3K4me and H3K4me2, respectively). We have previously reported potent (bis)urea and (bis)thiourea LSD1 inhibitors that increase cellular levels of H3K4me and H3K4me2, promote the re-expression of silenced tumor suppressor genes and suppress tumor growth in vitro. Here we report the design additional (bis)urea and (bis)thiourea LSD1 inhibitors that feature 3-5-3 or 3-6-3 carbon backbone architectures. Three of these compounds displayed single-digit IC50 values in a recombinant LSD1 assay. In addition, compound 6d exhibited an IC50 of 4.2μM against the Calu-6 human lung adenocarcinoma line, and 4.8μM against the MCF7 breast tumor cell line, in an MTS cell viability assay. Following treatment with 6b–6d, Calu-6 cells exhibited a significant increase in the mRNA expression for the silenced tumor suppressor genes SFRP2, HCAD and p16, and modest increases in GATA4 message. The compounds described in this paper represent the most potent epigenetic modulators in this series, and have potential for use as antitumor agents.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Novel 4-substituted-N,N-dimethyltetrahydronaphthalen-2-amines: synthesis,
           affinity, and in silico docking studies at serotonin 5-HT2-type and
           histamine H1 G protein-coupled receptors
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Rajeev Sakhuja , Krishnakanth Kondabolu , Tania Córdova-Sintjago , Sean Travers , Adam S. Vincek , Myong Sang Kim , Khalil A. Abboud , Lijuan Fang , Zhuming Sun , Clinton E. Canal , Raymond G. Booth
      Syntheses were undertaken of derivatives of (2S,4R)-(−)-trans-4-phenyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (4-phenyl-2-dimethylaminotetralin, PAT), a stereospecific agonist at the serotonin 5-HT2C G protein-coupled receptor (GPCR), with inverse agonist activity at 5-HT2A and 5-HT2B GPCRs. Molecular changes were made at the PAT C(4)-position, while preserving N,N-dimethyl substitution at the 2-position as well as trans-stereochemistry, structural features previously shown to be optimal for 5-HT2 binding. Affinities of analogs were determined at recombinant human 5-HT2 GPCRs in comparison to the phylogenetically closely-related histamine H1 GPCR, and in silico ligand docking studies were conducted at receptor molecular models to help interpret pharmacological results and guide future ligand design. In most cases, C(4)-substituted PAT analogs exhibited the same stereoselectivity ([−]-trans >[+]-trans) as the parent PAT across 5-HT2 and H1 GPCRs, albeit, with variable receptor selectivity. 4-(4′-substituted)-PAT analogs, however, demonstrated reversed stereoselectivity ([2S,4R]-[+]-trans >[2S,4R]-[−]-trans), with absolute configuration confirmed by single X-ray crystallographic data for the 4-(4′-Cl)-PAT analog. Pharmacological affinity results and computational results herein support further PAT drug development studies and provide a basis for predicting and interpreting translational results, including, for (+)-trans-4-(4′-Cl)-PAT and (−)-trans-4-(3′-Br)-PAT that were previously shown to be more potent and efficacious than their corresponding enantiomers in rodent models of psychoses, psychostimulant-induced behaviors, and compulsive feeding (‘binge-eating’).
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      PubDate: 2015-03-15T03:40:34Z
       
  • Discovery of anthranilamides as a novel class of inhibitors of neurotropic
           alphavirus replication
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Scott J. Barraza , Philip C. Delekta , Janice A. Sindac , Craig J. Dobry , Jianming Xiang , Richard F. Keep , David J. Miller , Scott D. Larsen
      Neurotropic alphaviruses are debilitating pathogens that infect the central nervous system (CNS) and are transmitted to humans via mosquitoes. There exist no effective human vaccines against these viruses, underlining the need for effective antivirals, but no antiviral drugs are available for treating infection once the viruses have invaded the CNS. Previously, we reported the development of novel indole-2-carboxamide-based inhibitors of alphavirus replication that demonstrate significant reduction of viral titer and achieve measurable brain permeation in a pharmacokinetic mouse model. Herein we report our continued efforts to improve physicochemical properties predictive of in vivo blood–brain barrier (BBB) permeability through reduction of overall molecular weight, replacing the indole core with a variety of aromatic and non-aromatic monocyclics. These studies culminated in the identification of simple anthranilamides that retain excellent potency with improved metabolic stability and significantly greater aqueous solubility. Furthermore, in a live virus study, we showed that two new compounds were capable of reducing viral titer by two orders of magnitude and that these compounds likely exert their effects through a mechanism similar to that of our indole-2-carboxamide inhibitors.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Synthesis, structural analysis and antitumor activity of novel
           17α-picolyl and 17(E)-picolinylidene A-modified androstane
           derivatives
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Jovana J. Ajduković , Katarina M. Penov Gaši , Dimitar S. Jakimov , Olivera R. Klisurić , Suzana S. Jovanović-Šanta , Marija N. Sakač , Lidija D. Aleksić , Evgenija A. Djurendić
      The heterocyclic ring at C-17 position of the androstane compounds plays an important role in biological activity. The aim of the present study was to synthesize and evaluate potential antitumor activity of different A-modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives. In several synthetic steps, novel derivatives bearing the hydroximino, nitrile or lactame functions in A-ring were synthesized and characterized according to the spectral data, by mass analysis as well as XRD analysis (compounds 6, 13 and 15). The structurally most promising compounds 6, 11–17 were investigated as antitumor agents. The in vitro antiproliferative activity was evaluated against six human cancer cell lines: estrogen receptor negative (ER−) breast adenocarcinoma (MDA-MB-231); estrogen receptor positive (ER+) breast adenocarcinoma (MCF-7); prostate cancer (PC-3); human cervical carcinoma (HeLa); lung adenocarcinoma (A549) and colon adenocarcinoma (HT-29) using MTT assay. The results of the 48h incubation time in vitro tests showed that compound 15 was the most effective against PC-3 (IC50 6.6μM), compound 17 against MCF-7 (IC50 7.9μM) cells, while compound 16 exhibited strong antiproliferative effect against both, MCF-7 (IC50 1.7μM) and PC-3 (IC50 8.7μM) cancer cells. It was also found that compounds 16 and 17 induced apoptosis in MCF-7 cells (dicyano derivative 17 stronger then dioxime 16 and reference formestane), with no distinct changes in the cell cycle of MCF-7 cells.
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      PubDate: 2015-03-15T03:40:34Z
       
  • 2-Benzisothiazolylimino-5-benzylidene-4-thiazolidinones as protective
           agents against cartilage destruction
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Lucia Crascì , Paola Vicini , Matteo Incerti , Venera Cardile , Sergio Avondo , Annamaria Panico
      We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs) 3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protective agents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulated by IL-1β. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs, was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover, selected derivatives 1h and 1g was studied for nuclear factor kappaB (NF-κB) inhibition by Western Blot analysis and for MMP-3 protein release using ELISA test. The structure–activity relationship of tested compounds demonstrates a favorable effect of the para substitution on the 5-benzilydene ring. Compound 1g shows a potent and selective activity on MMP-3 versus MMP-13. Accordingly, 1g possesses high antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production of MMPs and NF-κB expression. Thus 1g can be considered as new potential chondroprotective agents.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Molecular features and toxicological properties of four common pesticides,
           acetamiprid, deltamethrin, chlorpyriphos and fipronil
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Emiliane Taillebois , Zakaria Alamiddine , Christine Brazier , Jérôme Graton , Adèle D. Laurent , Steeve H. Thany , Jean-Yves Le Questel
      Structural features and selected physicochemical properties of four common pesticides: acetamiprid (neonicotinoid), chlorpyriphos (organophosphate insecticide), deltamethrin (pyrethroid) and fipronil (phenylpyrazole) have been investigated by Density Functional Theory quantum chemical calculations. The high flexible character of these insecticides is revealed by the numerous conformers obtained, located within a 20kJmol−1 range in the gas phase. In line with this trend, a redistribution of the energetic minima is observed in water medium. Molecular electrostatic potential calculations provide a ranking of the potential interaction sites of the four insecticides. The theoretical studies reported in the present work are completed by comparative toxicological assays against three aphid strains. Thus, the same toxicity order for the two susceptible strains Myzus persicae 4106A and Acyrthosiphon pisum LSR1: acetamiprid>fipronil>deltamethrin>chlorpyriphos is revealed. In the resistant strain M. persicae 1300145, the toxicity order is modified: acetamiprid>fipronil>chlorpyriphos>deltamethrin. Interestingly, the strain 1300145 which is known to be resistant to neonicotinoids, is also less sensitive to deltamethrin, chlorpyriphos and fipronil.
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      PubDate: 2015-03-15T03:40:34Z
       
  • N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors:
           Design, synthesis and antiplasmodial activity
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Marta Figueiras , Lis Coelho , Kathryn J. Wicht , Sofia A. Santos , João Lavrado , Jiri Gut , Philip J. Rosenthal , Fátima Nogueira , Timothy J. Egan , Rui Moreira , Alexandra Paulo
      We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres. 3-Chloro derivatives (10a–f) showed selectivity for malaria parasite compared to human cells, high activity against Plasmodium falciparum chloroquine (CQ)-resistant strain W2 (IC50s between 20 and 158nM), good correlation with β-hematin inhibition and improved vacuolar accumulation ratios, thus suggesting inhibition of Hz growth as one possible mechanism of action for these compounds. Moreover, our studies show that Hz is a valid target for the development of new antimalarials able to overcome CQ resistance.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Anti-trypanosomal cadinanes synthesized by transannular cyclization of the
           natural sesquiterpene lactone nobilin
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Maria De Mieri , Marcel Kaiser , Reto Brun , Ursula Thormann , Georgios Imanidis , Matthias Hamburger
      Acid-catalyzed transannular cyclization of the germacrene-type sesquiterpene lactone nobilin 1 was investigated with the aim of obtaining new anti-trypanosomal cadinane derivatives. The reaction was regiospecific in all tested reaction conditions. Compounds were fully characterized by spectroscopic and computational methods, and the anti-trypanosomal activity was evaluated and compared to nobilin (IC50 3.19±1.69μM). The tricyclic derivative 11 showed most potent in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms (IC50 0.46±0.01μM). Acid-catalyzed transannular cyclization of natural cyclodecadienes is an efficient strategy to generate new natural product derivatives with anti-protozoal activity.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Structure activity studies of nociceptin/orphanin FQ(1–13)-NH2
           derivatives modified in position 5
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Remo Guerrini , Erika Marzola , Claudio Trapella , Salvatore Pacifico , Maria Camilla Cerlesi , Davide Malfacini , Federica Ferrari , Mark Francis Bird , David George Lambert , Severo Salvadori , Girolamo Calo
      Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide acting as the endogenous ligand of the N/OFQ peptide receptor (NOP). N/OFQ(1–13)-NH2 is the shortest N/OFQ sequence maintaining the same potency and efficacy as the natural peptide. Thus N/OFQ(1–13)-NH2 was used as chemical template for investigating the structure activity relationship of threonine in position 5. 28 [X5]N/OFQ(1–13)-NH2 derivatives, in which Thr was substituted with natural and unnatural residues, were synthesized and characterized pharmacologically for their effects at the human NOP receptor. Two different functional assays were used: agonist stimulated [35S]GTPγS binding in cell membranes and calcium mobilization in whole cells co-expressing chimeric G proteins. All [X5]N/OFQ(1–13)-NH2 derivatives behaved as full NOP agonists showing large differences in their potency. There was an excellent correlation between the results obtained in the two assays. The results of this study suggest that: position 5 does not play a pivotal role in receptor activation; the secondary alcoholic function of Thr is not important for receptor binding; side chain size, lipo/hydrophilic balance as well as hydrogen bond capability are also not crucial for receptor binding; an aliphatic amino function positively charged with at least 3 carbon atom distance from the peptide backbone has a huge disrupting effect on receptor binding. In conclusion this study demonstrates that a simple ethyl side chain as in compound 23 is sufficient in N/OFQ position 5 for maintaining bioactivity.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Editorial board
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7




      PubDate: 2015-03-15T03:40:34Z
       
  • Graphical contents list
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7




      PubDate: 2015-03-15T03:40:34Z
       
  • Cannabidiol (CBD) and its analogs: a review of their effects on
           inflammation
    • Abstract: Publication date: 1 April 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 7
      Author(s): Sumner Burstein
      First isolated from Cannabis in 1940 by Roger Adams, the structure of CBD was not completely elucidated until 1963. Subsequent studies resulted in the pronouncement that THC was the ‘active’ principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD. This was no doubt due to the belief that activity meant psychoactivity that was shown by THC and not by CBD. In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years. In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed. Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD and combined THC plus CBD treatment.
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      PubDate: 2015-03-15T03:40:34Z
       
  • Dual Inhibition of Allosteric Mitogen-Activated Protein Kinase (MEK) and
           Phosphatidylinositol 3-Kinase (PI3K) Oncogenic Targets with a Bifunctional
           Inhibitor
    • Abstract: Publication date: Available online 6 March 2015
      Source:Bioorganic & Medicinal Chemistry
      Author(s): Marcian E. Van Dort , Stefanie Galbán , Hanxiao Wang , Judith Sebolt-Leopold , Christopher Whitehead , Hao Hong , Alnawaz Rehemtulla , Brian D. Ross
      The MAP kinase (Ras/MEK/ERK) and PI3K/Akt/mTOR oncogenic signaling pathways are central regulators of KRAS-mediated transformation. Molecular reciprocity between the Ras/MEK/ERK and PI3K/Akt/mTOR pathways provides cancer cells with the ability to evade treatment when targeting only one pathway with monotherapy. Multi-kinase targeting was explored through the development of a single bivalent chemical entity by covalent linking of high-affinity MEK and PI3K inhibitors. A prototype dual-acting agent (compound 8) designed using the PI3K inhibitor ZSTK474 and the Raf/MEK inhibitor RO5126766 as scaffolds displayed high in vitro inhibition of both PI3K (IC50 = 172 nM) and MEK1 (IC50 = 473 nM). Additionally, compound 8 demonstrated significant modulation of MEK and PI3K signaling pathway activity in human A549 human lung adenocarcinoma cells and pancreatic cancer cells (PANC-1) and also decreased cellular viability in these two cell lines.
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      PubDate: 2015-03-06T21:59:43Z
       
  • The use of a conformational cathepsin D-derived epitope for vaccine
           development against Schistosoma mansoni
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Abdullah A.H. Ahmad Fuaad , Romain Roubille , Mark S. Pearson , Darren A. Pickering , Alex C. Loukas , Mariusz Skwarczynski , Istvan Toth
      Schistosomiasis is caused by the infection from Schistosoma species. Among these, Schistosoma mansoni is one of the major species that infects millions of people worldwide. The use of praziquantel is effective in clearing the infestation but treatment of a large and widespread population in endemic areas is unsustainable. Thus, synergistic approach of using drug and vaccination can serve as an alternative to the current treatment. In this study, we have developed vaccine candidates that composed of three components: a B-cell epitope derived from S. mansoni cathepsin D protein (Sm-CatD) flanked by GCN4 helix promoting peptide; a promiscuous T-helper epitope (P25); and a lipid core peptide system, in attempt to develop self-adjuvanting vaccine candidates against the schistosome. Physicochemical properties of the vaccine candidates were analysed and antibodies to each construct were raised in BALB/c mice. The vaccine candidates were able to self-assemble into particles that induced high titres of IgG without the use of additional adjuvant. The antibody levels were comparable to that induced by peptide formulated with strong but toxic Freund’s adjuvant. The integration of a GCN4 sequence induced the helical conformation of the epitope, while the addition of the T helper peptide was very effective in inducing consistent IgG-specific antibodies response amongst mice. These findings are particularly encouraging for the development of efficient and immunogenic vaccine against schistosomiasis.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Design, synthesis and SAR studies of GABA uptake inhibitors derived from
           2-substituted pyrrolidine-2-yl-acetic acids
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Tobias Steffan , Thejavathi Renukappa-Gutke , Georg Höfner , Klaus T. Wanner
      In this paper, we disclose the design and synthesis of a series of 2-substituted pyrrolidine-2-yl-acetic acid as core structures and the N-arylalkyl derivatives thereof as potential GABA transport inhibitors. The 2-position in the side chain of pyrrolidine-2-yl-acetic acid derivatives was substituted with alkyl, hydroxy and amino groups to modulate the activity and selectivity to mGAT1 and mGAT4 proteins. SAR studies of the compounds performed for the four mouse GABA transporter proteins (mGAT1–mGAT4) implied significant potencies and subtype selectivities for 2-hydroxy-2-pyrrolidine-2-yl-acetic acid derivatives. The racemate rac-(u)-13c exhibited the highest potency (pIC50 5.67) at and selectivity for mGAT1 in GABA uptake assays. In fact, the potency of rac-(u)-13c at hGAT-1 (pIC50 6.14) was even higher than its potency at mGAT1. These uptake results for rac-(u)-13c are in line with the binding affinities to the aforesaid proteins mGAT1 (pK i 6.99) and hGAT-1 (pK i 7.18) determined by MS Binding Assay based on NO711 as marker quantified by LC–ESI-MS–MS analysis. Interestingly, the 2-hydroxy-2-pyrrolidine-2-yl-acetic acid rac-(u)-13d containing 2-{[tris(4-methoxyphenyl)]methoxy} ethyl group at the nitrogen atom of the pyrrolidine ring showed high potency at mGAT4 and a comparatively better selectivity for this protein (>15 against mGAT3) than the well known mGAT4 uptake inhibitor (S)-SNAP-5114.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Synthesis of dansyl-labeled probe of thiophene analogue of annonaceous
           acetogenins for visualization of cell distribution and growth inhibitory
           activity toward human cancer cell lines
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Naoto Kojima , Yuki Suga , Takuya Matsumoto , Tetsuaki Tanaka , Akinobu Akatsuka , Takao Yamori , Shingo Dan , Hiroki Iwasaki , Masayuki Yamashita
      The convergent synthesis of the dansyl-labeled probe of the thiophene-3-carboxamide analogue of annonaceous acetogenins, which shows potent antitumor activity, was accomplished by two asymmetric alkynylations of the 2,5-diformyl THF equivalent with an alkyne having a thiophene moiety and another alkyne tagged with a dansyl group. The growth inhibitory profiles toward 39 human cancer cell lines revealed that the probe retained the biological function of its mother compound, and would be useful for studying cellular activity.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Discovery and in vitro and in vivo profiles of
           N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide
           as a novel class of dual orexin receptor antagonist
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Ryo Suzuki , Dai Nozawa , Aya Futamura , Rie Nishikawa-Shimono , Masahito Abe , Nobutaka Hattori , Hiroshi Ohta , Yuko Araki , Daiji Kambe , Mari Ohmichi , Seiken Tokura , Takeshi Aoki , Norikazu Ohtake , Hiroshi Kawamoto
      Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2–1.4h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Design, synthesis, and biological evaluation of a series of bifunctional
           ligands of opioids/SSRIs
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Mehr-un-Nisa , Munawar A. Munawar , Yeon Sun Lee , David Rankin , Jawaria Munir , Josephine Lai , Misbahul A. Khan , Victor J. Hruby
      A series of opioid and serotonin re-uptake inhibitors (SSRIs) bifunctional ligands have been designed, synthesized, and tested for their activities and efficacies at μ-, δ- and κ opioid receptors and SSRIs receptors. Most of the compounds showed high affinities for μ- and δ-opioid receptors and lower affinities for SSRIs and κ opioid receptors. A docking study on the μ-opioid receptor binding pocket has been carried out for ligands 3–11. The ligands 7 and 11 have displayed the highest binding profiles for the μ-opioid receptor binding site with ΔG bind (−12.14kcal/mol) and K i value (1.0nM), and ΔG bind (−12.41kcal/mol) and K i value (0.4nM), respectively. Ligand 3 was shown to have the potential of dual acting serotonin/norepinephrine re-uptake inhibitor (SNRI) antidepressant activity in addition to opioid activities, and thus could be used for the design of multifunctional ligands in the area of a novel approach for the treatment of pain and depression.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Bis-3-chloropiperidines containing bridging lysine linkers: Influence of
           side chain structure on DNA alkylating activity
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Ivonne Zuravka , Rolf Roesmann , Alice Sosic , Richard Göttlich , Barbara Gatto
      A series of bis-3-chloropiperidines containing lysine linkers was synthesised as DNA alkylating model compounds by using a bidirectional synthetic strategy. These novel piperidine mustard based agents have been evaluated for their alkylating properties towards nucleic acids and were shown to alkylate and cleave DNA with strong preference for guanine residues. Our studies reveal that the introduction of aromatic groups in the side chain of the lysine linker has an impact on DNA alkylating activity. Analysis by ESI mass spectrometry enabled the verification of the reactive aziridinium ion formation. Overall, the results confirm our recently proposed reaction mechanism of bis-3-chloropiperidines.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • 6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as
           selective inhibitors of PI3Kα
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Yong Yin , Yan-Qing Zhang , Biao Jin , Shao Sha , Xun Wu , Chetan B. Sangani , She-Feng Wang , Fang Qiao , Ai-Min Lu , Peng-Cheng Lv , Hai-Liang Zhu
      Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3Kα, with the IC50 value of 0.016μM, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3Kβ. It indicated the potential of developing 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as the new PI3Kα selective inhibitors for tumor treatment.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • QSAR model as a random event: A case of rat toxicity
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Alla P. Toropova , Andrey A. Toropov , Emilio Benfenati , Danuta Leszczynska , Jerzy Leszczynski
      Quantitative structure—property/activity relationships (QSPRs/QSARs) can be used to predict physicochemical and/or biochemical behavior of substances which were not studied experimentally. Typically predicted values for chemicals in the training set are accurate since they were used to build the model. QSPR/QSAR models must be validated before they are used in practice. Unfortunately, the majority of the suggested approaches of the validation of QSPR/QSAR models are based on consideration of geometrical features of clusters of data points in the plot of experimental versus calculated values of an endpoint. We believe these geometrical criteria can be more useful if they are analyzed for several splits into the training and test sets. In this way, one can estimate the reproducibility of the model with various splits and better evaluate model reliability. The probability of the correct prediction of an endpoint for external validation set (in the series of the above-mentioned splits) can provide an useful way to evaluate the domain of applicability of the model.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
  • Synthesis and biological evaluation of 4-nitroindole derivatives as 5-HT2A
           receptor antagonists
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Faisal Hayat , Ambily Nath Indu Viswanath , Ae Nim Pae , Hyewhon Rhim , Woo-Kyu Park , Hea-Young Park Choo
      A novel series of 4-nitroindole sulfonamides containing a methyleneamino-N,N-dimethylformamidine were prepared. The binding of these compounds to 5-HT2A and 5-HT2C was evaluated, and most of the compounds showed IC50 values of less than 1μM, and exhibited high selectivity for the 5-HT2C receptor. However, little selectivity was observed in the functional assay for 5-HT6 receptors. The computational modeling studies further validated the biological results and also demonstrated a reasonable correlation between the activity of compounds and the mode of superimposition with specified pharmacophoric features.
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      PubDate: 2015-02-27T08:28:43Z
       
  • Editorial board
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6




      PubDate: 2015-02-27T08:28:43Z
       
  • Graphical contents list
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6




      PubDate: 2015-02-27T08:28:43Z
       
  • Synthesis of the O-linked hexasaccharide containing
           β-d-Galp-(1→2)-d-Galf in Trypanosoma cruzi mucins. Differences
           on sialylation by trans-sialidase of the two constituent hexasaccharides
    • Abstract: Publication date: 15 March 2015
      Source:Bioorganic & Medicinal Chemistry, Volume 23, Issue 6
      Author(s): Rosalía Agustí , M. Eugenia Giorgi , Verónica M. Mendoza , Gustavo A. Kashiwagi , Rosa M. de Lederkremer , Carola Gallo-Rodriguez
      The hexasaccharide β-d-Galp-(1→2)-[β-d-Galp-(1→3)]-β-d-Galp-(1→6)-[β-d-Galp(1→2)-β-d-Galf(1→4)]-d-GlcNAc (10) and its β-d-Galf-(1→2)-β-d-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. The terminal β-d-Galp units are sites of sialylation by the parasite trans-sialidase. Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. The 1H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose.
      Graphical abstract image

      PubDate: 2015-02-27T08:28:43Z
       
 
 
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