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  Subjects -> CHEMISTRY (Total: 845 journals)
    - ANALYTICAL CHEMISTRY (51 journals)
    - CHEMISTRY (595 journals)
    - CRYSTALLOGRAPHY (21 journals)
    - ELECTROCHEMISTRY (25 journals)
    - INORGANIC CHEMISTRY (41 journals)
    - ORGANIC CHEMISTRY (45 journals)
    - PHYSICAL CHEMISTRY (67 journals)

CHEMISTRY (595 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 8)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26)
ACS Catalysis     Full-text available via subscription   (Followers: 34)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 24)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 246)
ACS Photonics     Full-text available via subscription   (Followers: 11)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 8)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 51)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 56)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 15)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 21)
Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 41)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 27)
American Journal of Plant Physiology     Open Access   (Followers: 14)
American Mineralogist     Hybrid Journal   (Followers: 14)
Analyst     Full-text available via subscription   (Followers: 40)
Angewandte Chemie     Hybrid Journal   (Followers: 199)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 218)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 4)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 15)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 310)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 1)
Biomacromolecules     Full-text available via subscription   (Followers: 19)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 118)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 91)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
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: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 3)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 4)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 66)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 7)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 8)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 4)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 14)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 72)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 24)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 20)
Chemical Reviews     Full-text available via subscription   (Followers: 181)
Chemical Science     Open Access   (Followers: 22)
Chemical Technology     Open Access   (Followers: 16)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 8)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 58)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 26)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 146)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 20)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 255)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 9)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Clay Minerals     Full-text available via subscription   (Followers: 10)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 7)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 18)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 2)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 17)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 61)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 4)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 3)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Elements     Full-text available via subscription   (Followers: 3)
Environmental Chemistry     Hybrid Journal   (Followers: 7)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)

        1 2 3 | Last

Journal Cover Bioorganic Chemistry
  [SJR: 0.926]   [H-I: 43]   [10 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0045-2068 - ISSN (Online) 1090-2120
   Published by Elsevier Homepage  [3051 journals]
  • Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as
           microtubule targeting and apoptosis inducing agents
    • Authors: Faria Sultana; Srinivasa Reddy Bonam; V. Ganga Reddy; V. Lakshma Nayak; Ravikumar Akunuri; Sunitha Rani Routhu; Abdullah Alarifi; M. Sampath Kumar Halmuthur; Ahmed Kamal
      Pages: 1 - 12
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Faria Sultana, Srinivasa Reddy Bonam, V. Ganga Reddy, V. Lakshma Nayak, Ravikumar Akunuri, Sunitha Rani Routhu, Abdullah Alarifi, M. Sampath Kumar Halmuthur, Ahmed Kamal
      A series of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates (5a-aa) were designed, synthesized and evaluated for their cytotoxic potency against a panel of human cancer cell lines like lung (A-549), breast (MDA MB-231), prostrate (DU-145) and colon cancer (HT-29). Preliminary results revealed that some of these conjugates like 5d and 5u exhibited significant antiproliferative effect against human breast cancer (MDA MB-231) with IC50 values of 1.3 and 1.2 µM respectively. To investigate the mechanistic aspects underlying the activity, the detailed biological studies of these promising conjugates (5d and 5u) were carried out on the MDA MB-231 cancer cells. Flow cytometric analysis revealed that these conjugates induce cell-cycle arrest in the G2/M phase. The tubulin polymerization assay suggests that these conjugates effectively inhibit microtubule assembly. In addition, morphological changes, reactive oxygen species (ROS) detection by 2′, 7′–dichlorofluorescin diacetate (DCFDA) and annexin V–FITC/PI assays indicate that 5d and 5u induces apoptosis. Furthermore, in silico computational studies, including molecular docking studies have been carried out to rationalise the binding modes of these conjugates with the tubulin protein.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.019
      Issue No: Vol. 76 (2017)
       
  • Structural modeling of osteoarthritis ADAMTS4 complex with its cognate
           inhibitory protein TIMP3 and rational derivation of cyclic peptide
           inhibitors from the complex interface to target ADAMTS4
    • Authors: Wei Zhang; Biao Zhong; Chi Zhang; Yukai Wang; Shang Guo; Congfeng Luo; Yulin Zhan
      Pages: 13 - 22
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Wei Zhang, Biao Zhong, Chi Zhang, Yukai Wang, Shang Guo, Congfeng Luo, Yulin Zhan
      The ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) enzyme is a matrix-associated zinc metalloendopeptidase that plays an essential role in the degradation of cartilage aggrecan in arthritic diseases and has been recognized as one of the most primary targets for therapeutic intervention in osteoarthritis (OA). Here, we reported computational modeling of the atomic-level complex structure of ADAMTS4 with its cognate inhibitory protein TIMP3 based on high-resolution crystal template. By systematically examining the modeled complex structure we successfully identified a short inhibitory loop (62EASESLC68) in TIMP3 N-terminal inhibitory domain (NID) that directly participates in blocking the enzyme’s active site, which, and its extended versions, were then broken from the full-length protein to serve as the peptide inhibitor candidates of ADAMTS4. Atomistic molecular dynamics simulation, binding energetic analysis, and fluorescence-based assay revealed that the TIMP3-derived linear peptides can only bind weakly to the enzyme (K d = 74 ± 8 μM), which would incur a considerable entropy penalty due to the high conformational flexibility and intrinsic disorder of these linear peptides. In this respect, we proposed a cyclization strategy to improve enzyme–peptide binding affinity by, instead of traditionally maximizing enthalpy contribution, minimizing entropy cost of the binding, where a disulfide bond was added across the two terminal residues of linear peptides, resulting in a number of TIMP3-derived cyclic peptides. Our studies confirmed that the cyclization, as might be expected, can promote peptide binding capability against ADAMTS4 substantially, with affinity increase by 3-fold, 9-fold and 7-fold for cyclic peptides , and , respectively.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.017
      Issue No: Vol. 76 (2017)
       
  • Efficient one-pot enzymatic synthesis of dephospho coenzyme A
    • Authors: Krishna Sapkota; Faqing Huang
      Pages: 23 - 27
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Krishna Sapkota, Faqing Huang
      Dephospho coenzyme A (depCoA) is the last intermediate for CoA biosynthesis, and it can be used as a transcription initiator to prepare CoA-linked RNA by in vitro transcription. However, commercially available depCoA is expensive. We hereby describe a simple and efficient enzymatic synthesis of depCoA in a single-step from commercially available and inexpensive oxidized pantethine (Ox-Pan) and ATP. A plasmid (pCoaDAa) was constructed to co-express and co-purify two enzymes pantothenate kinase (PanK/coaA) and phosphopantetheine adenylyltransferase (PPAT/coaD). Starting from Ox-Pan and ATP, two different synthetic routes of one-pot reaction catalyzed by PanK and PPAT, followed by a simple column purification step, afforded depCoA and its oxidized dimer (Ox-depCoA) with high yields and purity. The simplicity and low cost of our method should make depCoA easily accessible to a broad scientific community, and promote research on CoA-related areas in biology and biomedicine.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.012
      Issue No: Vol. 76 (2017)
       
  • Chemical characterization of cytotoxic indole acetic acid derivative from
           mulberry fruit (Morus alba L.) against human cervical cancer
    • Authors: Jae Sik Yu; Dahae Lee; Seoung Rak Lee; Jae Wook Lee; Chang-Ik Choi; Tae Su Jang; Ki Sung Kang; Ki Hyun Kim
      Pages: 28 - 36
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Jae Sik Yu, Dahae Lee, Seoung Rak Lee, Jae Wook Lee, Chang-Ik Choi, Tae Su Jang, Ki Sung Kang, Ki Hyun Kim
      The fruit of the white mulberry tree (Morus alba L.) is a multiple fruit with a sweet flavor commonly consumed around the world. Chemical investigation of the fruits led to the isolation of two indole acetic acid derivatives (1 −2) including a new compound, which turned out to be an isolation artifact, 3S-(β-D-glucopyranosyloxy)-2,3-dihydro-2-oxo-1H-indole-3-acetic acid butyl ester (1), along with five known compounds (3 −7). Compounds 2 and 7 were newly identified from mulberry fruit. The new isolation artifact (1) exhibited cytotoxic effect on human cervical cancer Hela cells in a dose-dependent manner. Compound 1 activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Simultaneous alterations in protein expression of mitochondrial factors Bax, BID and Bcl-2 were also observed. A comparison between compounds 1 and 2 led to a structure-activity relationship analysis of the cytotoxic effect. These results suggest that compound 1 could be beneficial in human cervical cancer treatment, and provide a theoretical basis for further application of compound 1.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.015
      Issue No: Vol. 76 (2017)
       
  • 5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones: As potent urease
           inhibitors; synthesis, in vitro screening, and molecular modeling study
    • Authors: Shahbaz Shamim; Khalid Mohammed Khan; Uzma Salar; Farman Ali; Muhammad Arif Lodhi; Muhammad Taha; Farman Ali Khan; Sajda Ashraf; Zaheer Ul-Haq; Muhammad Ali; Shahnaz Perveen
      Pages: 37 - 52
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Shahbaz Shamim, Khalid Mohammed Khan, Uzma Salar, Farman Ali, Muhammad Arif Lodhi, Muhammad Taha, Farman Ali Khan, Sajda Ashraf, Zaheer Ul-Haq, Muhammad Ali, Shahnaz Perveen
      5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones 1–43 were synthesized in a “one-pot” three component reaction and structurally characterized by various spectroscopic techniques such as 1H, 13C NMR, EI-MS, HREI-MS, and IR. All compounds were evaluated for their in vitro urease inhibitory activity. It is worth mentioning that except derivatives 1, 11, 12, and 14, all were found to be more potent than the standard thiourea (IC50 = 21.25 ± 0.15 µM) and showed their urease inhibitory potential in the range of IC50 = 3.70 ± 0.5–20.14 ± 0.1 µM. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules. However, molecular modeling study was performed to confirm the binding interactions of the molecules (ligand) with the active site of enzyme.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.021
      Issue No: Vol. 76 (2017)
       
  • Nitric oxide inhibitors with a spiro diterpenoid skeleton from Scutellaria
           formosana: Structures, NO inhibitory effects, and interactions with iNOS
    • Authors: Peixia Wang; Xueyuan Yang; Feng Liu; Yue Liang; Guochen Su; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Yuanqiang Guo
      Pages: 53 - 60
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Peixia Wang, Xueyuan Yang, Feng Liu, Yue Liang, Guochen Su, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo
      A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of five new spiro diterpenoids (1 −5) from the aerial parts of Scutellaria formosana. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The nitric oxide (NO) inhibitory effects were evaluated and all of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.008
      Issue No: Vol. 76 (2017)
       
  • Improving the carbonic anhydrase inhibition profile of the sulfamoylphenyl
           pharmacophore by attachment of carbohydrate moieties
    • Authors: Leonardo E. Riafrecha; Silvia Bua; Claudiu T. Supuran; Pedro A. Colinas
      Pages: 61 - 66
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Leonardo E. Riafrecha, Silvia Bua, Claudiu T. Supuran, Pedro A. Colinas
      One of the most successful approaches for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was denominated ‘the sugar approach’. The sugar approach consists in attaching different carbohydrates to CA inhibiting pharmacophores for modulating the physicochemical properties of these pharmacological agents. In line with this approach, in this paper, we present a new class of C-glycosides incorporating the sulfamoylphenyl moiety. These compounds have been prepared by sulfamoylation of C-glycosyl phenols, which have been synthetized by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. The inhibition profile of the new glycomimetics was determined against four human (h) CA isozymes, comprising hCAs I and II (cytosolic, ubiquitous isozymes), hCA IV and hCA IX (tumor associated isozyme). Peracetylated and deprotected C-glycosyl sulfamates showed better inhibition selectivity compared to structurally related phenylsulfamates. In this study, deprotected compound 12 was identified as selective inhibitor of hCA IX. These results confirm that attaching carbohydrate moieties to CA sulfamoylphenyl pharmacophore improves its inhibitory activity.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.020
      Issue No: Vol. 76 (2017)
       
  • N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-β-alanines and their
           derivatives as inhibitors of human carbonic anhydrases
    • Authors: Irena Vaškevičienė; Vaida Paketurytė; Asta Zubrienė; Kristina Kantminienė; Vytautas Mickevičius; Daumantas Matulis
      Pages: 16 - 29
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Irena Vaškevičienė, Vaida Paketurytė, Asta Zubrienė, Kristina Kantminienė, Vytautas Mickevičius, Daumantas Matulis
      A series of N-substituted and N,N-disubstituted β-amino acids and their derivatives bearing benzenesulfonamide moiety were designed and synthesized in search of compounds that would be high-affinity and selective inhibitors of human carbonic anhydrases (CA). There are 12 catalytically active human CA isoforms, the cytosolic CA I, CA II, CA III, CA VII, and CA XIII, secreted CA VI, the mitochondrial CA VA and CA VB, membrane-associated CA IV, and transmembrane CA IX, CA XII, and CA XIV. The di-bromo meta-substituted compounds exhibited low nanomolar dissociation constants and over 10-fold selectivity for mitochondrial isozyme CA VB, implicated in diseases of the central nervous system and obesity. These compounds can be used for further development as inhibitors of significant binding affinity and selectivity towards CA VB isozyme.
      Graphical abstract image

      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.08.017
      Issue No: Vol. 75 (2017)
       
  • Synthesis of thiobarbituric acid derivatives: In vitro α-glucosidase
           inhibition and molecular docking studies
    • Authors: Assem Barakat; M. Ali; Abdullah Mohammed Al-Majid; Sammer Yousuf; M. Iqbal Choudhary; Ruqaiya Khalil; Zaheer Ul-Haq
      Pages: 99 - 105
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Assem Barakat, M. Ali, Abdullah Mohammed Al-Majid, Sammer Yousuf, M. Iqbal Choudhary, Ruqaiya Khalil, Zaheer Ul-Haq
      Synthesis, structure, and evaluation of in vitro α-glucosidase enzyme inhibition of a new class of diethylammonium salts of aryl substituted thiobarbituric acid is described. This protocol is straight, environmentally benign and efficient, involving Aldol-Michael addition reaction in one pot fashion. The 3D chemical structures of the synthesized compounds were assigned based on spectroscopic methods and X-ray single crystal diffraction analyses. All synthesized compounds 3a-3n were evaluated for their in vitro α-glucosidase enzyme inhibitory activity, whereas acarbose was used as the standard drug (IC50 =840±1.73µM). All tested compounds were found to possess varying degree of α-glucosidase enzyme inhibition activity with (IC50 =19.46±1.84–415.8±4.0µM). Compound 3i (IC50 =19.4±1.84µM) exhibited the highest activity. To the best of knowledge this is the first report of the in vitro α-glucosidase enzyme inhibition by the diethylamonium salts of aryl substituted thiobarbituric acid. Furthermore, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites.
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      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.003
      Issue No: Vol. 75 (2017)
       
  • Molecular docking and QSAR analyses of aromatic heterocycle
           thiosemicarbazone analogues for finding novel tyrosinase inhibitors
    • Authors: Huanhuan Dong; Jing Liu; Xiaoru Liu; Yanying Yu; Shuwen Cao
      Pages: 106 - 117
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Huanhuan Dong, Jing Liu, Xiaoru Liu, Yanying Yu, Shuwen Cao
      A collection of 36 thiosemicarbazone analogues possessed a broad span of tyrosinase inhibitory activities was designed and obtained. Robust and reliable CoMFA and CoMSIA models were gained to predict the structure–activity relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend upon molecular shape, size, and charge. The sterically bulky group at the C-4 position of the thiophene ring contributed a high capacity for biological activity. Some bulky substituents at the C1-position and C12-position, and electron-negative groups at the C3-position, helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and detailed information about binding mode, affinity, and the principal mechanism between the ligands and tyrosinase. Based on these, a prospective structure modification and optimization of the most potent compound, T32, was suggested for further research.
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      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.07.002
      Issue No: Vol. 75 (2017)
       
  • Novel Diphenylthiazole Derivatives with Multi-Target Mechanism: Synthesis,
           Docking study, Anticancer and Anti-Inflammatory Activities
    • Authors: Ahmed H. Abdelazeem; Mohammed T. El-Saadi; Eman G. Said; Bahaa G.M. Youssif; Hany A. Omar; Samir M. El-Moghazy
      Pages: 127 - 138
      Abstract: Publication date: Available online 12 September 2017
      Source:Bioorganic Chemistry
      Author(s): Ahmed H. Abdelazeem, Mohammed T. El-Saadi, Eman G. Said, Bahaa G.M. Youssif, Hany A. Omar, Samir M. El-Moghazy
      Over the last few decades, a growing body of studies addressed the anticancer activity of NSAIDs, particularly selective COX-2 inhibitors. However, their exact molecular mechanism still unclear and not fully investigated. In this regard, a novel series of compounds bearing a COXs privilege scaffold, diphenyl thiazole, was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines. The most active compounds 10b, 14a,b, 16a, 17a,b and 18b were evaluated in vitro for COX-1/COX-2 inhibitory activity. These compounds were suggested to exert their anticancer activity through a multi-target mechanism based on their structural features. Thus, compounds 10b and 17b with the least IC50 values in MTT assay were tested against three known anticancer targets; EGFR, BRAF and tubulin. Compounds 10b and 17b showed remarkable activity against EGFR with IC50 values of 0.4 and 0.2 μM, respectively and good activity against BRAF with IC50 values of 1.3 and 1.7 μM, respectively. In contrast, they showed weak activity in tubulin polymerization assay. The in vivo anti-inflammatory potential was assessed and interestingly, compound 17b was the most potent compound. Together, this study offers some important insights into the correlation between COXs inhibition and cancer treatment. Additionally, the results demonstrated the promising activity of these compounds with a multi-target mechanism as good candidates for further development into potential anticancer agents.
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      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.009
      Issue No: Vol. 75 (2017)
       
  • Design, synthesis, and evaluation of novel ursolic acid derivatives as
           HIF-1α inhibitors with anticancer potential
    • Authors: Ke-Qiang Chi; Zhi-Yu Wei; Ke-Si Wang; Jie Wu; Wei-Qiang Chen; Xue-Jun Jin; Hu-Ri Piao
      Pages: 157 - 169
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Ke-Qiang Chi, Zhi-Yu Wei, Ke-Si Wang, Jie Wu, Wei-Qiang Chen, Xue-Jun Jin, Hu-Ri Piao
      Hypoxia-inducible factor-1α (HIF-1α), a key mediator in tumor metastasis and angiogenesis, is associated with poor patient prognosis and has been recognized as an important cancer drug target. In this work, four novel series of ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were designed, synthesized, and evaluated for anti-tumor activity as HIF-1α inhibitors. The majority of the compounds showed an excellent ability to inhibit the expression of HIF-1α. In particular, 11b inhibited HIF-1α transcriptional activity under hypoxic conditions with IC50 =36.9μM. The cytotoxicity of these compounds was also assessed in human colon cancer cell HCT116 cells by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50 >100μmol/L), which was lower than that of ursolic acid (IC50 =23.8μmol/L). The mechanism of action of the representative compound 11b was also investigated.
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      PubDate: 2017-09-25T22:32:31Z
      DOI: 10.1016/j.bioorg.2017.09.013
      Issue No: Vol. 75 (2017)
       
  • Acyl selenoureido benzensulfonamides show potent inhibitory activity
           
    • Authors: Andrea Angeli; Ghulam Abbas; Sonia Del Prete; Fabrizio Carta; Clemente Capasso; Claudiu T. Supuran
      Pages: 170 - 172
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Andrea Angeli, Ghulam Abbas, Sonia Del Prete, Fabrizio Carta, Clemente Capasso, Claudiu T. Supuran
      A series of acyl selenoureido benzensulfonamides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against two Vibrio cholerae such enzymes (VchCAα over VchCAβ) belonging to the α- and β-classes, potential novel targets for anti-infective drugs development. These compounds showed strong inhibitory action against VchCAα over VchCAβ and excellent selectivity over the human (h) off-target isoforms hCA I and II. Identification of potent and possibly selective inhibitors of VchCAα and/or VchCAβ over the human counterparts may lead to pharmacological tools useful for understanding the physiological role(s) of these under-investigated proteins, possibly involved in the virulence of the bacterium and colonization of the host in bicarbonate rich regions of the gastro-intestinal tract.
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      PubDate: 2017-09-25T22:32:31Z
      DOI: 10.1016/j.bioorg.2017.09.016
      Issue No: Vol. 75 (2017)
       
  • Reactivity improvement of cellulolytic enzyme lignin via mild hydrothermal
           modification
    • Authors: Zhuoming Ma; Jiafa Tang; Shujun Li; Enxiang Suo
      Pages: 173 - 180
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Zhuoming Ma, Jiafa Tang, Shujun Li, Enxiang Suo
      Isolated by the cellulolytic enzyme lignin (CEL) process, water-alcohol (1:1, v/v) was introduced as co-solvent in the process of the hydrothermal treatment. The modification parameters such as reaction temperature and time, solid-to-liquid ratio, and catalysts (NaOH and NaOAlO2) have been investigated in terms of the specific lignin properties, such as the phenolic hydroxyl content (OHphen), DPPH free radical scavenging rate, and formaldehyde value. The CELs were also characterized by GPC, FT-IR and 1 H NMR spectroscopy, and Py-GC/MS. The key data are under optimal lignin modification conditions (solid-to-liquid ratio of 1:10 (w/v) and a temperature of 250°C for 60min) are: OHphen content: 2.50mmol/g; half maximal inhibitory concentration (IC50) towards DPPH free radicals: 88.2mg/L; formaldehyde value: 446.9g/kg). Both base catalysts decrease the residue rate, but phenol reactivities of the products were also detracted. Py-GC/MS results revealed that modified lignin had a higher phenolic composition than the CEL did, especially the modified lignin without catalyst (ML), which represented 74.51% phenolic content.
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      PubDate: 2017-10-04T07:32:12Z
      DOI: 10.1016/j.bioorg.2017.09.014
      Issue No: Vol. 75 (2017)
       
  • Chemical synthesis and in silico molecular modeling of novel pyrrolyl
           benzohydrazide derivatives: Their biological evaluation against enoyl ACP
           reductase (InhA) and Mycobacterium tuberculosis
    • Authors: Shrinivas D. Joshi; Uttam A. More; Sheshagiri R. Dixit; Sunil V. Balmi; Basavaraj G. Kulkarni; Geeta Ullagaddi; Christian Lherbet; Tejraj M. Aminabhavi
      Pages: 181 - 200
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Shrinivas D. Joshi, Uttam A. More, Sheshagiri R. Dixit, Sunil V. Balmi, Basavaraj G. Kulkarni, Geeta Ullagaddi, Christian Lherbet, Tejraj M. Aminabhavi
      In efforts to develop new antitubercular agents, we report here the synthesis of a series of novel pyrrole hydrazine derivatives. The molecules were evaluated against inhibitors of InhA, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of the mycobacterial cell wall as well as inhibitors of Mycobacterium tuberculosis H37Rv. The binding mode of compounds at the active site of enoyl-ACP reductase was explored using the surflex-docking method. The model suggests one or two H-bonding interactions between the compounds and the InhA enzyme. Some compounds exhibited good activities against InhA in addition to promising activities against M. tuberculosis.
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      PubDate: 2017-10-04T07:32:12Z
      DOI: 10.1016/j.bioorg.2017.09.008
      Issue No: Vol. 75 (2017)
       
  • Synthesis and cholinesterase inhibitory activity study of new piperidone
           grafted spiropyrrolidines
    • Authors: Alireza Basiri; Basma M. Abd Razik; Mohammed Oday Ezzat; Yalda Kia; Raju Suresh Kumar; Abdulrahman I. Almansour; Natarajan Arumugam; Vikneswaran Murugaiyah
      Pages: 210 - 216
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Alireza Basiri, Basma M. Abd Razik, Mohammed Oday Ezzat, Yalda Kia, Raju Suresh Kumar, Abdulrahman I. Almansour, Natarajan Arumugam, Vikneswaran Murugaiyah
      Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 µM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.09.019
      Issue No: Vol. 75 (2017)
       
  • The anthraquinone emodin inhibits the non-exported FIKK kinase from
           Plasmodium falciparum
    • Authors: Benjamin C. Lin; Darcy R. Harris; Lucy M.D. Kirkman; Astrid M. Perez; Yiwen Qian; Janse T. Schermerhorn; Min Y. Hong; Dennis S. Winston; Lingyin Xu; Alexander M. Lieber; Matthew Hamilton; Gabriel S. Brandt
      Pages: 217 - 223
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Benjamin C. Lin, Darcy R. Harris, Lucy M.D. Kirkman, Astrid M. Perez, Yiwen Qian, Janse T. Schermerhorn, Min Y. Hong, Dennis S. Winston, Lingyin Xu, Alexander M. Lieber, Matthew Hamilton, Gabriel S. Brandt
      The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50 =2μM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.09.011
      Issue No: Vol. 75 (2017)
       
  • Novel quinoline incorporating 1,2,4-triazole/oxime hybrids: Synthesis,
           molecular docking, anti-inflammatory, COX inhibition, ulceroginicity and
           histopathological investigations
    • Authors: Aliaa M. Mohassab; Heba A. Hassan; Dalia Abdelhamid; Mohamed Abdel-Aziz; Kevin N. Dalby; Tamer S. Kaoud
      Pages: 242 - 259
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Aliaa M. Mohassab, Heba A. Hassan, Dalia Abdelhamid, Mohamed Abdel-Aziz, Kevin N. Dalby, Tamer S. Kaoud
      A series of novel quinolines incorporating 1,2,4-triazole/oxime hybrids were prepared. They showed remarkable anti-inflammatory activity and exhibited very low incidence of gastric ulceration, compared to indomethacin. Most of the compounds tested showed remarkable inhibition of the COX-1 isozyme, with IC50’s ranging from 0.48 to 28µM. Compounds 7c and 9g showed high safety profiles with normal stomach tissue integrity. Docking studies supported the observed in vitro inhibitory activity towards the COX enzymes that may explain their promising anti-inflammatory activity relative to indomethacin. Moreover, differences between the COX-1 and COX-2 isozymes in observed energy scores, as well as in the number of interactions with some of the compounds tested, might predict their higher selectivity towards COX-1 rather than COX-2. Compound 9e was found to inhibit both COXs non-competitively with Ki values of 81µM and 94.6µM.
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      PubDate: 2017-10-14T08:14:15Z
      DOI: 10.1016/j.bioorg.2017.09.018
      Issue No: Vol. 75 (2017)
       
  • Inactivation of bovine plasma amine oxidase by
           1,1,1–trihalo–3–aminopropanes
    • Authors: Jisook Kim; Irene N. Lee
      Pages: 265 - 273
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Jisook Kim, Irene N. Lee
      In this paper, we report the inactivation of copper containing bovine plasma amine oxidase (BPAO) by a series of saturated alkylamines containing halogen atoms at γ-position, which are 1,1,1-trihalo-3-aminopropane, 1,1,1-trifluoro-2-hydroxy-3-aminopropane, 1,1,1-trichloro-2-hydroxy-3-aminopropane, and 1,1,1-trichloro-2-(2-phenethyloxy)-3-aminopropane. The trihalo-2-hydroxypropylamine analogs exhibited a time-dependent inactivation behavior of BPAO, with 1,1,1-trifluoro-2-hydroxy-3-aminopropane as the most efficient inactivator. The incorporation of a OH group at β-position increased inactivation efficiency by 10-fold within the trifluoro analogs, and the incorporation of a phenethyloxy group at β-position exhibited a higher efficiency by 3-fold within the trichloro analogs based on I75 values. All four compounds were found to be irreversible inactivators for BPAO.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.007
      Issue No: Vol. 75 (2017)
       
  • New iridoid glycosides from the fruits of Forsythia suspensa and their
           hepatoprotective activities
    • Authors: Si-Yuan Shao; Ya-Nan Yang; Zi-Ming Feng; Jian-Shuang Jiang; Pei-Cheng Zhang
      Pages: 303 - 309
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Si-Yuan Shao, Ya-Nan Yang, Zi-Ming Feng, Jian-Shuang Jiang, Pei-Cheng Zhang
      A novel iridoid glycoside trimer named forsydoitriside A (1) and five new iridoid glycosides (2–6) were isolated from the fruits of Forsythia suspensa together with two known compounds (7, 8). These new structures were elucidated by comprehensive spectroscopic data and the comparison of experimental and calculated electronic circular dichroism spectra. Compounds 1–8 were all assayed on acetaminophen-induced HepG2 cell damage. The results exhibited that compounds 2, 3, 5 and 6 possessed strong hepatoprotective activities against the damage in HepG2 cell.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.006
      Issue No: Vol. 75 (2017)
       
  • Application of the Morita-Baylis-Hillman reaction in the synthesis of
           3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1
           integrase inhibitors
    • Authors: Khethobole C. Sekgota; Swarup Majumder; Michelle Isaacs; Dumisani Mnkandhla; Heinrich C. Hoppe; Setshaba D. Khanye; Frederik H. Kriel; Judy Coates; Perry T. Kaye
      Pages: 310 - 316
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Khethobole C. Sekgota, Swarup Majumder, Michelle Isaacs, Dumisani Mnkandhla, Heinrich C. Hoppe, Setshaba D. Khanye, Frederik H. Kriel, Judy Coates, Perry T. Kaye
      A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.09.015
      Issue No: Vol. 75 (2017)
       
  • Syntheses of 4,6-dihydroxypyrimidine diones, their urease inhibition, in
           vitro, in silico, and kinetic studies
    • Authors: Munira Taj Muhammad; Khalid Mohammed Khan; Arshia; Ajmal Khan; Fiza Arshad; Bibi Fatima; M. Iqbal Choudhary; Naima Syed; Syed Tarique Moin
      Pages: 317 - 331
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Munira Taj Muhammad, Khalid Mohammed Khan, Arshia, Ajmal Khan, Fiza Arshad, Bibi Fatima, M. Iqbal Choudhary, Naima Syed, Syed Tarique Moin
      A library of 4,6-dihydroxypyrimidine diones (1–35) were synthesized and evaluated for their urease inhibitory activity. Structure-activity relationships, and mechanism of inhibition were also studied. All compounds were found to be active with IC50 values between 22.6±1.14–117.4±0.73µM, in comparison to standard, thiourea (IC50 =21.2±1.3µM). Kinetics studies on the most active compounds 2–7, 16, 17, 28, and 33 were performed to investigate their modes of inhibition, and dissociation constants Ki . Compounds 2, 3, 7, 16, 28, and 33 were found to be mixed-type of inhibitors with Ki values in the range of 7.91±0.024–13.03±0.013µM, whereas, compounds 4–6, and 17 were found to be non-competitive inhibitors with Ki values in the range of 9.28±0.019–13.05±0.023µM. In silico study was also performed, and a good correlation was observed between experimental and docking studies. This study is continuation of our previously reported urease inhibitory activity of pyrimidine diones, representing potential leads for further research as possible treatment of diseases caused by ureolytic bacteria.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.08.018
      Issue No: Vol. 75 (2017)
       
  • Is the Sudlow site I of human serum albumin more generous to adopt
           prospective anti-cancer bioorganic compound than that of bovine: A
           combined spectroscopic and docking simulation approach
    • Authors: Ritika Joshi; Manojkumar Jadhao; Himank Kumar; Sujit Kumar Ghosh
      Pages: 332 - 346
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Ritika Joshi, Manojkumar Jadhao, Himank Kumar, Sujit Kumar Ghosh
      A comparative biophysical study on the individual conformational adaptation embraced by two homologous serum albumins (SA) (bovine and human) towards a potential anticancer bioorganic compound 2-(6-chlorobenzo[d] thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)- dione (CBIQD) is apparent from the discrimination in binding behavior and the ensuing consequences accomplished by combined in vitro optical spectroscopy, in silico molecular docking and molecular dynamics (MD) simulation. The Sudlow site I of HSA although anion receptive, harbors neutral CBIQD in Sudlow site I (subdomain IIA, close to Trp) of HSA, while in BSA its prefers to snugly fit into Sudlow site II (subdomain IIIA, close to Tyr). Based on discernable diminution of HSA mean fluorescence lifetime as a function of biluminophore concentration, facile occurrence of fluorescence resonance energy transfer (FRET) is substantiated as the probable quenching mechanism accompanied by structural deformations in the protein ensemble. CBIQD establishes itself within HSA close to Trp214, and consequently reduces the micropolarity of the cybotactic environment that is predominantly constituted by hydrophobic amino acid residues. The stronger association of CBIQD with HSA encourages an allosteric modulation leading to slight deformation in its secondary structure whereas for BSA the association is comparatively weaker. Sudlow site I of HSA is capable to embrace a favorable conformation like malleable gold to provide room for incoming CBIQD, whereas for BSA it behaves more like rigid cast-iron which does not admit any change thus forcing CBIQD to occupy an altogether different binding location i.e. the Sudlow site II. The anticancer CBIQD is found to be stable within the HSA scaffold as vindicated by root mean square deviation (RMSD) and root mean square fluctuation (RMSF) obtained by MD simulation. A competitively inhibited esterase-like activity of HSA upon CBIQD binding to Lys199 and Arg257 residues, plausibly envisions that similar naphthalimide based prodrugs, bearing ester functionality, can be particularly activated by Sudlow site I of HSA. The consolidated spectroscopic research described herein may encourage design of naphthalimide based pro-drugs for effective in vivo biodistribution using HSA-based drug delivery systems.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.013
      Issue No: Vol. 75 (2017)
       
  • Enzymatic synthesis of 1,3-dihydroxyphenylacetoyl-sn-glycerol:
           Optimization by response surface methodology and evaluation of its
           antioxidant and antibacterial activities
    • Authors: Nadia Kharrat; Imen Aissa; Youssef Dgachi; Fatma Aloui; Fakher Chabchoub; Mohamed Bouaziz; Youssef Gargouri
      Pages: 347 - 356
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Nadia Kharrat, Imen Aissa, Youssef Dgachi, Fatma Aloui, Fakher Chabchoub, Mohamed Bouaziz, Youssef Gargouri
      In this study, the enzymatic synthesis of phenylacetoyl glycerol ester was carried out as a response to the increasing consumer demand for natural compounds. 1,3-dihydroxyphenylacetoyl-sn-Glycerol (1,3-di-HPA-Gly), labeled as “natural” compound with interesting biological properties, has been successfully synthesized for the first time in good yield by a direct esterification of glycerol (Gly) with p-hydroxyphenylacetic acid (p-HPA) using immobilized Candida antarctica lipase as a biocatalyst. Spectroscopic analyses of purified esters showed that the glycerol was mono- or di-esterified on the primary hydroxyl group. These compounds were evaluated for their antioxidant activity using two different tests. The glycerol di-esters (1,3-di-HPA-Gly) showed a higher antiradical capacity than that of the butyl hydroxytoluene. Furthermore, compared to the p-HPA, synthesized ester (1,3-di-HPA-Gly) exhibited the most antibacterial effect mainly against Gram + bacteria. Among synthesized esters the 1,3-di-HPA-Gly was most effective as antioxidant and antibacterial compound. These findings could be the basis for a further exploitation of the new compound, 1,3-di-HPA-Gly, as antioxidant and antibacterial active ingredient in the cosmetic and pharmaceutical fields.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.011
      Issue No: Vol. 75 (2017)
       
  • Discovery of triazole-based uracil derivatives bearing amide moieties as
           novel dipeptidyl peptidase-IV inhibitors
    • Authors: Xiaoyan Deng; Li Han; Jinpei Zhou; Huibin Zhang; Qing Li
      Pages: 357 - 367
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Xiaoyan Deng, Li Han, Jinpei Zhou, Huibin Zhang, Qing Li
      Dipeptidyl peptidase-IV (DPP-4) is a validated target for T2DM treatment. We previously reported a novel series of triazole-based uracil derivatives bearing aliphatic carboxylic acids with potent DPP-4 inhibitory activities in vitro, but these compounds showed poor hypoglycemic effects in vivo. Herein we further optimized the triazole moiety by amidation of the carboxylic acid to improve in vivo activities. Two series of compounds 3a-f and 4a-g were designed and synthesized. By screening in DPP-4, compound 4c was identified as a potent DPP-4 inhibitor with the IC50 value of 28.62 nM. Docking study revealed compound 4c has a favorable binding mode and interpreted the SAR of these analogs. DPP-8 and DPP-9 tests indicated compound 4c had excellent selectivity over DPP-8 and DPP-9. Further in vivo evaluations revealed that compound 4c showed more potent hypoglycemic activity than its corresponding carboxylic acid in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice. The overall results have shown that compound 4c could be a promising lead for further development of novel DPP-4 agents treating T2DM.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.010
      Issue No: Vol. 75 (2017)
       
  • Novel quinoline-3-carboxamides (Part 2): Design, optimization and
           synthesis of quinoline based scaffold as EGFR inhibitors with potent
           anticancer activity
    • Authors: Rasha M. Aly; Rabah A.T. Serya; Amira M. El-Motwally; Ahmed Esmat; Safinaz Abbas; Dalal A. Abou El Ella
      Pages: 368 - 392
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Rasha M. Aly, Rabah A.T. Serya, Amira M. El-Motwally, Ahmed Esmat, Safinaz Abbas, Dalal A. Abou El Ella
      EGFR has a key role in cell growth. Its mutation and overexpression share in epithelial malignancies and tumor growth. Quinazoline and quinoline derivatives are common anticancer intracellular inhibitors of EGFR kinase, and their optimization is an important issue for development of potent targeted anticancer agents. Based on these facts, different strategies were used for optimizing our reported quinoline-3-carboxamide compound III (EGFR IC50 = 5.283 µM and MCF-7 IC50 = 3.46 µM) through different molecular modeling techniques. The optimized compounds were synthesized and subjected to EGFR binding assay and accordingly some more potent inhibitors were obtained. The most potent quinoline-3-carboxamides were the furan derivative 5o; thiophene derivative 6b; and benzyloxy derivative 10 showing EGFR IC50 values 2.61, 0.49 and 1.73 μM, respectively. Furthermore, the anticancer activity of compounds eliciting potent EGFR inhibition (5o, 5p, 6b, 8a, 8b, and 10) was evaluated against MCF-7 cell line where they exhibited IC50 values 3.355, 3.647, 5.069, 3.617, 0.839 and 10.85 μM, respectively. Compound 6b was selected as lead structure for further optimization hoping to produce more potent EGFR inhibitors.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.018
      Issue No: Vol. 75 (2017)
       
  • Hit discovery of
           4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel
           EGFR inhibitor from a designed small library
    • Authors: Ahmed Elkamhawy; Sora Paik; Ahmed H.E. Hassan; Yong Sup Lee; Eun Joo Roh
      Pages: 393 - 405
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Ahmed Elkamhawy, Sora Paik, Ahmed H.E. Hassan, Yong Sup Lee, Eun Joo Roh
      Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC50 1.05–5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.009
      Issue No: Vol. 75 (2017)
       
  • Synthetic and medicinal perspective of thiazolidinones: A review
    • Authors: Sundeep Kaur Manjal; Ramandeep Kaur; Rohit Bhatia; Kapil Kumar; Virender Singh; Ravi Shankar; Rupinder Kaur; Ravindra K. Rawal
      Pages: 406 - 423
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Sundeep Kaur Manjal, Ramandeep Kaur, Rohit Bhatia, Kapil Kumar, Virender Singh, Ravi Shankar, Rupinder Kaur, Ravindra K. Rawal
      In the modern scenario, thiazolidinone scaffold has emerged as a very potent scaffold as per its clinical significance concerned. It has attracted the keen interest of the researchers due to its great diversity in biological activities. Thiazolidinones are the saturated form of thiazole, called thiazolidine with a carbonyl group. The 1,3-thiazolidin-4-ones possess wide range of pharmacological activities such as anti-cancer, anti-diabetic, anti-microbial, anti-viral, anti-inflammatory and anti-convulsant. In the past few years, various newer synthetic approaches have been designed to synthesize diverse scaffolds to explore the various types of biological activities. In this review, an attempt has been made by the authors to summarize various synthetic strategies for thiazolidinone derivatives as well as their biological significance.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.014
      Issue No: Vol. 75 (2017)
       
  • Synthesis and bioelectrochemical behavior of aromatic amines
    • Authors: Muhammad Shabbir; Zareen Akhter; Iqbal Ahmad; Safeer Ahmed; Michael Bolte; Hammad Ismail; Bushra Mirza
      Pages: 102 - 111
      Abstract: Publication date: Available online 4 October 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Shabbir, Zareen Akhter, Iqbal Ahmad, Safeer Ahmed, Michael Bolte, Vickie McKee
      Four aromatic amines 1-amino-4-phenoxybenzene (A1), 4-(4-aminophenyloxy) biphenyl (A2), 1-(4-aminophenoxy) naphthalene (A3) and 2-(4-aminophenoxy) naphthalene (A4) were synthesized and characterized by elemental, spectroscopic (FTIR, NMR), mass spectrometric and single crystal X-ray diffraction methods. The compounds crystallized in monoclinic crystal system with space group P21. Intermolecular hydrogen bonds were observed between the amine group and amine/ether acceptors of neighboring molecules. Electrochemical investigations were done using cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV). CV studies showed that oxidation of aromatic amines takes place at about 0.9 V (vs. Ag/AgCl) and the electron transfer (ET) process has irreversible nature. After first scan reactive intermediate were generated electrochemically and some other cathodic and anodic peaks also appeared in the succeeding scans. DPV study revealed that ET process is accompanied by one electron. DNA binding study of aromatic amines was performed by CV and UV-visible spectroscopy. These investigations revealed groove binding mode of interaction of aromatic amines with DNA.
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      PubDate: 2017-10-04T07:32:12Z
      DOI: 10.1016/j.ica.2017.04.034
      Issue No: Vol. 463 (2017)
       
  • Issue TOC
    • Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75


      PubDate: 2017-11-16T03:53:07Z
       
  • Design, Synthesis, Anti-inflammatory Antitumor Activities, Molecular
           Modeling and Molecular Dynamics Simulations of Potential Naprosyn®
           Analogs as COX-1 and/or COX-2 Inhibitors
    • Authors: Mardia T. El Sayed; Marwa A.M.Sh. El-Sharief; Eman S. Zare; Nesrin M. Morsy; Ahmed R. Elsheakh; Mohammed Nayel; Hatem A. Abdel-Aziz; Andrey Voronkov; Vladimir Berishvili; Nermien M. Sabry; Ghada S. Hassan
      Abstract: Publication date: Available online 13 November 2017
      Source:Bioorganic Chemistry
      Author(s): Mardia T. El Sayed, Marwa A.M.Sh. El-Sharief, Eman S. Zare, Nesrin M. Morsy, Ahmed R. Elsheakh, Mohammed Nayel, Hatem A. Abdel-Aziz, Andrey Voronkov, Vladimir Berishvili, Nermien M. Sabry, Ghada S. Hassan
      Inflammation is a fundamental physiological process that is essential for survival of human being but at the same time is one of the major causes of human morbidity and mortality. In the past decade, numerous advances have taken place in the understanding and development of novel anti-inflammatory drugs. Therefore, investigation of newest anti-inflammatory agents is still a major challenge. In this study, novel and successfully synthesized naproxen-derivatives indicated powerful anti-inflammatory properties as potent of COX-1 and/or COX-2 inhibitors are reported. Results obtained revealed the presence of very potent derivatives with% inhibition of the oedema by 100% in addition to enzyme inhibition values that can reach 92%. The molecular docking and molecular dynamic calculations have been studied. Thus, new potent candidates for further investigation as prospective non-steroidal anti-inflammatory drug were proposed. Furthermore, twenty of the synthesized derivatives have been selected by the NCI, USA for anti-cancer screening and some of the tested compounds showed good% growth inhibition and some selectivity against some cell lines such as melanoma, non-small cell lung and colon cancer with GI% values ranging from 60.9-82.8%. Structure activity relationship has been performed and molecular modeling studies and molecular dynamic simulations have been performed for more explanation of the action of the synthesized compounds.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.11.002
       
  • Biocatalytic hydrolysis of chlorinated nicotinamides by a superior AS
           family amidase and its application in enzymatic production of
           2-chloronicotinic acid
    • Authors: Ren-Chao Zheng; Jian-Qiang Jin; Zhe-Ming Wu; Xiao-Ling Tang; Li-Qun Jin; Yu-Guo Zheng
      Abstract: Publication date: Available online 7 November 2017
      Source:Bioorganic Chemistry
      Author(s): Ren-Chao Zheng, Jian-Qiang Jin, Zhe-Ming Wu, Xiao-Ling Tang, Li-Qun Jin, Yu-Guo Zheng
      2-Chloronicotinic acid (2-CA) is an important building block for a series of agrochemicals and pharmaceuticals. Amidase-catalyzed hydrolysis of 2-chloronicotinamide is one of the most attractive approaches for 2-CA production. However, development of the bioprocess was plagued by low activity of amidase for 2-chloronicotinamide. In this work, an amidase signature (AS) family amidase from Pantoea sp. (Pa-Ami), with superior activity for nicotinamide and its chlorinated derivatives, was exploited and characterized. Kinetic analysis and molecular docking clearly indicated that chlorine substitution in the pyridine ring of nicotinamide, especially the substitution at 2-position led to a dramatic decrease of Pa-Ami activity. The productivity of the bioprocess was significantly improved using fed-batch mode at low reaction temperature and 2-CA was produced as high as 370 mM with a substrate conversion of 94.2%. These results imply that Pa-Ami is potentially promising biocatalyst for industrial production of 2-CA.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.11.001
       
  • Heterocyclic Periphery in the Design of Carbonic Anhydrase Inhibitors:
           1,2,4-Oxadiazol-5-yl Benzenesulfonamides as Potent and Selective
           Inhibitors of Cytosolic hCA II and Membrane-Bound hCA IX Isoforms
    • Authors: Mikhail Krasavin; Anton Shetnev; Tatyana Sharonova; Sergey Baykov; Tiziano Tuccinardi; Stanislav Kalinin; Andrea Angeli; Claudiu T. Supuran
      Abstract: Publication date: Available online 16 October 2017
      Source:Bioorganic Chemistry
      Author(s): Mikhail Krasavin, Anton Shetnev, Tatyana Sharonova, Sergey Baykov, Tiziano Tuccinardi, Stanislav Kalinin, Andrea Angeli, Claudiu T. Supuran
      A series of novel aromatic primary sulfonamides decorated with diversely substituted 1,2,4-oxadiazole periphery groups has been prepared using a parallel chemistry approach. The compounds displayed a potent inhibition of cytosolic hCA II and membrane-bound hCA IX isoforms. Due to a different cellular localization of the two target enzymes, the compounds can be viewed as selective inhibition tools for either isoform, depending on the cellular permeability profile. The SAR findings revealed in this study has been well rationalized by docking simulation of the key compounds against the crystal structures of the relevant hCA isoforms.
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      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.005
       
  • Coumarinyl pyranopyrimidines as new neuropeptide S receptor antagonists;
           design, synthesis, homology and molecular docking
    • Authors: Rasha Z. Batran; Dina H. Dawood; Samia A. El-Seginy; Timothy J. Maher; Kuljeet S. Gugnani; Alejandro N. Rondon-Ortiz
      Abstract: Publication date: Available online 12 October 2017
      Source:Bioorganic Chemistry
      Author(s): Rasha Z. Batran, Dina H. Dawood, Samia A. El-Seginy, Timothy J. Maher, Kuljeet S. Gugnani, Alejandro N. Rondon-Ortiz
      In this work, we described the design, synthesis and characterization of a new class of NPSR antagonists bearing the tetracyclic coumarinyl pyranopyrimidine scaffold incorporated with different acyclic and / or heterocyclic moieties. These compounds are highlighted in this study as never being used as NPSR antagonists before which provides a model for the discovery of new bioactive inhibitors that may hold potential for drug development towards anxiety, food, and addiction disorders. Synthetic and medicinal chemistry studies led to the identification of four potent antagonists, compounds 7d, 10, 12 and 13, which were able to significantly inhibit the stimulatory effect of NPS through counteracting the increased intracellular Ca2+ accumulation. The target compound 7d was the most active derivative behaving as a pure NPSR antagonist and displaying IC50 value of 2 μM. Homology model of NPSR receptor was built based on bovine rhodopsin structure. Modeling studies were carried out to further rationalize the NPSR binding mode of the target compounds. Moreover, molecular dynamics simulation study was performed for compounds 7d, 10 and 12 which revealed the stability of the ligand-protein complex and the reliability of the docking studies.
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      PubDate: 2017-10-14T08:14:15Z
      DOI: 10.1016/j.bioorg.2017.09.017
       
  • 3,4-Dimethoxybenzohydrazide derivatives as antiulcer: Molecular Modeling
           and Density Functional Studies
    • Authors: Muhammad Taha; Hadiani Ismail Hamizah Mohd Zaki Abdul Wadood Hassane
      Abstract: Publication date: Available online 7 October 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Nor Hadiani Ismail, Hamizah Mohd Zaki, Abdul Wadood, El Hassane Anouar, Syahrul Imran, Bohari M. Yamin, Fazal Rahim, Muhammad Ali, Khalid Mohammed Khan
      3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2, 3, 4 and 5 with IC50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC50 value 21.40 ± 0.21 µM). Compounds 1, 6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1H-NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.
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      PubDate: 2017-10-11T07:58:32Z
       
  • Sulfonyl Hydrazones Derived from 3-Formylchromone as Non-Selective
           Inhibitors of MAO-A and MAO-B: Synthesis, Molecular Modelling andIn-Silico
           ADME Evaluation
    • Authors: Syed Mobasher Ali Abid; Hafiza Amna Younus; Mariya al-Rashida; Zunaira Arshad; Tooba Maryum; Mazhar Amjad Gilani; Abdulrahman I. Alharthi; Jamshed Iqbal
      Abstract: Publication date: Available online 4 October 2017
      Source:Bioorganic Chemistry
      Author(s): Syed Mobasher Ali Abid, Hafiza Amna Younus, Mariya al-Rashida, Zunaira Arshad, Tooba Maryum, Mazhar Amjad Gilani, Abdulrahman I. Alharthi, Jamshed Iqbal
      A series of sulfonyl hydrazones derived from 3-formylchromone was synthesized and discovered to be effective, non-selective inhibitors of monoamine oxidases (MAO-A and MAO-B). The compounds are easily (synthetically) accessible in high yields, by simple condensation of 4-methylbenzenesulfonohydrazide with different (un)substituted 3-formylchromones. All compounds had IC50 values in lower micro-molar range (IC50 = 0.33-7.14 μM for MAO-A, and 1.12-3.56 μM for MAO-B). The most active MAO-B inhibitor was N'-[(E)-(6-fluoro-4-oxo-4H-chromen-3-yl)methylidene]-4-methylbenzenesulfonohydrazide (3e) with IC50 value of 1.12±0.02 μM, and N'-[(E)-(6-chloro-4-oxo-4H-chromen-3-yl)methylidene]-4-methylbenzenesulfonohydrazide (3f) was the most active MAO-A inhibitor with IC50 value of 0.33±0.01 μM. From enzyme kinetic studies, the mode of inhibition against MAO-B was found to be competitive, whereas against MAO-A, it was found to be non-competitive. Molecular docking studies indicated a new binding pocket for non-competitive MAO-A inhibitors. The activity of these compounds is optimally combined with highly favorable ADME profile with predicted good oral bioavailability.
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      PubDate: 2017-10-11T07:58:32Z
      DOI: 10.1016/j.bioorg.2017.10.001
       
  • Cytotoxic dihydrobenzofuran neolignans from Mappianthus iodoies
    • Authors: Zhi-Hua Jiang; Yan-Ping Liu Ze-Hao Huang Ting-Ting Wang Xing-Yang Feng
      Abstract: Publication date: Available online 4 October 2017
      Source:Bioorganic Chemistry
      Author(s): Zhi-Hua Jiang, Yan-Ping Liu, Ze-Hao Huang, Ting-Ting Wang, Xing-Yang Feng, Hao Yue, Wei Guo, Yan-Hui Fu
      Three new dihydrobenzofuran neolignans, mappiodoinins A-C (1-3), together with nine known analogues (4-12) were isolated from the stems and leaves of Mappianthus iodoies. Their structures with the absolute configurations were elucidated by extensive spectroscopic methods. This is the first time to find dihydrobenzofuran neolignans from the genus Mappianthus. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW-480 in vitro. Neolignans 1-12 showed significant cytotoxic effects against various human cancer cell lines with IC50 values ranging from 0.16 to 18.62 μM.
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      PubDate: 2017-10-04T07:32:12Z
       
  • Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone
           derivatives: Effective agents against acetylcholinesterase
    • Authors: Cintia A. Menéndez; Brunella Biscussi; Sebastián Accordino; A. Paula Murray; Darío C. Gerbino; Gustavo A. Appignanesi
      Abstract: Publication date: Available online 22 September 2017
      Source:Bioorganic Chemistry
      Author(s): Cintia A. Menéndez, Brunella Biscussi, Sebastián Accordino, A. Paula Murray, Darío C. Gerbino, Gustavo A. Appignanesi
      The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46–12.09 μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered as a potential lead compound towards new drugs for the treatment of Alzheimer’s disease.
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      PubDate: 2017-09-25T22:32:31Z
      DOI: 10.1016/j.bioorg.2017.09.012
       
  • The inhibitory activity of HL-7 and HL-10 peptide from scorpion venom
           (Hemiscorpius lepturus) on angiotensin converting enzyme: Kinetic and
           docking study
    • Authors: Zahra Setayesh-Mehr; Ahmad Asoodeh
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Zahra Setayesh-Mehr, Ahmad Asoodeh
      The hypertension is one of the highest risk factors for stroke, myocardial infarction, vascular disease and chronic kidney disease. Angiotensin converting enzyme (ACE) has an important role in the physiological regulation of cardiovascular system. ACE inhibition is a key purpose for hypertension treatment. In this study, two peptides named HL-7 with the sequence of YLYELAR (MW: 927.07Da) and HL-10 with the sequence of AFPYYGHHLG (MW: 1161.28Da) were identified from scorpion venom of H. lepturus. The inhibitory activity of HL-7 and HL-10 was examined on rabbit ACE. The inhibition mechanisms were assayed by kinetic and docking studies. The IC50 values for ACE inhibition of HL-7 and HL-10 were 9.37µM and 17.22µM, respectively. Lineweaver-Burk plots showed that two peptides inhibited rabbit ACE with competitive manner. The molecular docking conformed experimental results and showed that the two peptides interacted with N-domain and C-domain active sites. Also, docking study revealed that the two peptides can form hydrogen and hydrophobic bonds at their binding sites. Both peptides had higher affinity to N-domain. Our results showed that HL-7 exhibited more strong interactions with amino acids at active site. It seems that HL-10 peptide could occupy more space, thereby inhibiting the substrate entrance to active site.
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      PubDate: 2017-09-13T12:08:47Z
       
  • Synthesis and in vitro Study of Benzofuran Hydrazone Derivatives as Novel
           Alpha-Amylase Inhibitor
    • Authors: Muhammad Taha; Syed Adnan Ali Shah; Syahrul Imran; Muhammad Afifi; Sridevi Chigurpati; Manikandan Selvaraj; Fazal Rahim; Hayat Ullah; Khalid Zaman; Shantini Vijayabalan
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Syed Adnan Ali Shah, Syahrul Imran, Muhammad Afifi, Sridevi Chigurpati, Manikandan Selvaraj, Fazal Rahim, Hayat Ullah, Khalid Zaman, Shantini Vijayabalan
      The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC50 value ranging between 1.078±0.19 to 2.926±0.05 µM when compared with acarbose having IC50= 0.62±0.22 µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.002
       
  • Nitric oxide inhibitory daphnane diterpenoids as potential
           anti-neuroinflammatory agents for AD from the twigs of Trigonostemon
           thyrsoideus
    • Authors: Feng Liu; Xueyuan Yang; Jun Ma; Yuling Yang; Chunfeng Xie; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Yuanqiang Guo
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Feng Liu, Xueyuan Yang, Jun Ma, Yuling Yang, Chunfeng Xie, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo
      The extensive pathology studies revealed that Alzheimer’s disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1−4) and eight known (5−12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1−4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.007
       
  • New indole-based chalconoids as tubulin-targeting antiproliferative agents
    • Authors: Hassan Mirzaei; Mohammad Shokrzadeh; Mona Modanloo; Ali Ziar; Gholam Hossein Riazi; Saeed Emami
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Hassan Mirzaei, Mohammad Shokrzadeh, Mona Modanloo, Ali Ziar, Gholam Hossein Riazi, Saeed Emami
      Tubulin-targeting compounds have a broad anticancer spectrum and are an important class of chemotherapeutic agents. Due to the importance of 3-bromo-3,5-dimethoxyphenyl scaffold in the anticancer activity of microtubule inhibitors such as crolibulin (EPC2407), we introduced this functionality into the indole-derived chalcones. Thus, we describe here the synthesis and biological evaluation of new indole-based chalconoids as tubulin-targeting antiproliferative agents. The best result was obtained by compound 9b against A549 cell with IC50 of 4.3 µg/mL, being more potent than the reference drug etoposide. Further biological evaluations revealed that compound 9b can inhibit tubulin polymerization and decrease the mitochondrial thiol content, resulting the induction of apoptosis in cancer cells. Docking studies with tubulin indicated that compound 9b could bind to the colchicine binding site.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.005
       
  • Traditional Chinese Medicinal Herbs as potential AChE inhibitors for
           anti-Alzheimer’s Disease: A review
    • Authors: Yingying Jiang; Hongwei Gao; Gulmira Turdu
      Abstract: Publication date: Available online 6 September 2017
      Source:Bioorganic Chemistry
      Author(s): Yingying Jiang, Hongwei Gao, Gulmira Turdu
      Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting 25 million people worldwide, and cholinergic hypothesis is considered as an important hypotheses in the processes of improving cognitive function and recognition skills in recent years. For the long-term treatment of AD, traditional Chinese medicine are particularly suitable for drug discovery. In this review, we sum up six traditional Chinese medicinal herbs concerned with development of AChEIs, including Herba Epimedii, Coptis Chinensis Franch, Rhizoma Curcumae Longae, Green tea, Ganoderma, Panax Ginseng. The listed compounds based on these herbs are belonging to six classes Flavonoids, Alkaloids, Ketones, Polyphenols, Terpenoid and Saponins, respectively. These compounds could be very promising agents in the search for potent anti-Alzheimer’s drugs.
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      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.09.004
       
  • Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum:
           structures, PTP1B inhibitory activities, and interactions with PTP1B
    • Authors: Xiangrong Cao; Xueyuan Yang; Peixia Wang; Yue Liang; Feng Liu; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Yuanqiang Guo
      Abstract: Publication date: Available online 6 September 2017
      Source:Bioorganic Chemistry
      Author(s): Xiangrong Cao, Xueyuan Yang, Peixia Wang, Yue Liang, Feng Liu, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo
      Protein tyrosine phosphatase 1B (PTP1B) has been regarded as a target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A−D (1−4) from the aerial parts of Hypericum longistylum. The structures of 1−4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1−4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.
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      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.09.001
       
  • Identification of new potent inhibitor of aldose reducatse from Ocimum
           basilicum
    • Authors: Huma Aslam Bhatti; Yildiz Tehseen; Kiran Maryam; Maliha Uroos; Bina S. Siddiqui; Abdul Hameed; Jamshed Iqbal
      Abstract: Publication date: Available online 5 September 2017
      Source:Bioorganic Chemistry
      Author(s): Huma Aslam Bhatti, Yildiz Tehseen, Kiran Maryam, Maliha Uroos, Bina S. Siddiqui, Abdul Hameed, Jamshed Iqbal
      Recent efforts is to develop cure for chronic diabetic complications results in the discovery of potent inhibitors against aldose reductase (AKR1B1, EC 1.1.1.21) whose role in diabetes is well-evident. In the present work, two new natural products were isolated from the ariel part of Ocimum basilicum;7-(3-hydroxypropyl)-3-methyl-8-β-O-D-glucoside-2H-chromen-2-one (1) and E-4-(6'-hydroxyhex-3'-en-1-yl)phenyl propionate (2) and confirmed their structures with different spectroscopic techniques including NMR spectroscopy etc. The isolated compounds (1, 2) were evaluated for in vitro inhibitory activity against aldose reductase (AKR1B1) and aldehyde reductase (AKR1A1). The natural product (1) showed better inhibitory activity for AKR1B1 with IC50 value of 2.095 ± 0.77 µM compare to standard sorbinil (IC50 = 3.14 ± 0.02 µM). Moreover, the compound (1) also showed multifolds higher activity (IC50 = 0.783 ± 0.07 µM) against AKR1A1 as compared to standard valproic acid (IC50 = 57.4 ± 0.89 µM). However, the natural product (2) showed slightly lower activity for AKR1B1 (IC50 = 4.324 ± 1.25 µM). Moreover, the molecular docking studies of the potent inhibitors were also performed to identify the putative binding modes within the active site of aldose/aldehyde reductases.
      Graphical abstract image

      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.08.011
       
  • Exploration of thioxothiazolidinone–sulfonate conjugates as a new class
           of aldehyde/aldose reductase inhibitors: A synthetic and computational
           investigation
    • Authors: Hina Andleeb; Yildiz Tehseen; Farrukh Jabeen; Imtiaz Khan; Jamshed Iqbal; Shahid Hameed
      Abstract: Publication date: Available online 31 August 2017
      Source:Bioorganic Chemistry
      Author(s): Hina Andleeb, Yildiz Tehseen, Farrukh Jabeen, Imtiaz Khan, Jamshed Iqbal, Shahid Hameed
      In the present study, the pharmacophore integration methodology provided an efficient access to a new library of thioxothiazolidinone–sulfonate conjugates (8a–r) from easily available synthetic precursors. The approach was excellently high yielding with flexible structural sites for chemical modifications. The designed hybrid scaffolds were assessed for aldehyde/aldose reductase inhibition activities. The results for the in vitro bioassays were promising with the identification of compound 8e as the lead and selective candidate for ALR2 inhibition with an IC50 value of 0.468 ± 0.003 µM as compared to 3.1 ± 0.2 µM for the standard (sorbinil), whereas compound 8o demonstrated high inhibitory potency for both ALR2 and ALR1 enzymes. Molecular modeling analysis of the potent compounds provided further insight into the biological properties where detailed binding mode analysis revealed that the conjugates (8a–r) were found stabilized in the active site of the enzymes through the development of a number of interactions with catalytic residues.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.009
       
  • SAR studies of some acetophenone phenylhydrazone based pyrazole
           derivatives as anticathepsin agents
    • Authors: Neera Raghav; Mamta Singh
      Abstract: Publication date: Available online 31 August 2017
      Source:Bioorganic Chemistry
      Author(s): Neera Raghav, Mamta Singh
      Cathepsins have emerged as promising molecular targets in a number of diseases such as Alzeimer’s, inflammation and cancer. Elevated cathepsin’s levels and decreased cellular inhibitor concentrations have emphasized the search for novel inhibitors of cathepsins. The present work is focused on the design and synthesis of some acetophenone phenylhydrazone based pyrazole derivatives as novel non peptidyl inhibitors of cathepsins B, H and L. The synthesized compounds after characterization have been explored for their inhibitory potency against cathepsins B, H and L. The results show that some of the synthesized compounds exhibit anti-catheptic activity with Ki value of the order of 10-10 M. Differential inhibitory effects have been observed for cathepsins B, H and L. Cathepsin L is inhibited more pronounced than cathepsin B and cathepsin H in that order.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.006
       
  • Liquid phase combinatorial synthesis of 1,2,5-trisubstituted benzimidazole
           derivatives as human DHODH inhibitors
    • Authors: Nikum D. Sitwala; Vivek K. Vyas; Bhavesh C. Variya; Snehal S. Patel; Chirag C. Mehta; Dharmraj N. Rana; Manjunath D. Ghate
      Abstract: Publication date: Available online 30 August 2017
      Source:Bioorganic Chemistry
      Author(s): Nikum D. Sitwala, Vivek K. Vyas, Bhavesh C. Variya, Snehal S. Patel, Chirag C. Mehta, Dharmraj N. Rana, Manjunath D. Ghate
      The synthesis of 1,2,5-trisubstituted benzimidazole derivatives was carried out using liquid phase combinatorial approach using soluble polymer assisted support (PEG5000). Synthesized compounds were characterized by FTIR, ESI-MS, 1H NMR and 13C NMR. The purity of compounds were confirmed with HPLC analysis. Compounds were also docked into the binding site of human dihydroorotate dehydrogenase (hDHODH). The synthesized compounds were screened for hDHODH enzyme inhibition assay using brequinar as standard compound. The synthesized compounds demonstrated comparative biological activity. Synthesized compound 8d and 8e demonstrated IC50 value of 81±2 nM and 97±2 nM, respectively.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.016
       
  • Phytochemicals with NO inhibitory effects and interactions with iNOS
           protein from Trigonostemon howii
    • Authors: Jun Ma; Xueyuan Yang; Peixia Wang; Bangjian Dong; Guochen Su; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Jianping Lin; Yuanqiang Guo
      Abstract: Publication date: Available online 24 August 2017
      Source:Bioorganic Chemistry
      Author(s): Jun Ma, Xueyuan Yang, Peixia Wang, Bangjian Dong, Guochen Su, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Jianping Lin, Yuanqiang Guo
      A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1−3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.008
       
 
 
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