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  Subjects -> CHEMISTRY (Total: 852 journals)
    - ANALYTICAL CHEMISTRY (52 journals)
    - CHEMISTRY (598 journals)
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    - PHYSICAL CHEMISTRY (69 journals)

CHEMISTRY (598 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 10)
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: 38)
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: 252)
ACS Photonics     Full-text available via subscription   (Followers: 12)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 23)
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 Chimica Slovenica     Open Access  
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: 57)
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: 18)
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)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
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: 66)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 15)
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: 39)
Angewandte Chemie     Hybrid Journal   (Followers: 179)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 229)
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: 16)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal   (Followers: 1)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 22)
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: 326)
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: 120)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 85)
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: 5)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 68)
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: 5)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 15)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 70)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 25)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 21)
Chemical Reviews     Full-text available via subscription   (Followers: 184)
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: 56)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 24)
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: 42)
Chemistry of Materials     Full-text available via subscription   (Followers: 246)
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: 14)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 10)
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: 6)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 19)
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: 11)
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)
Corrosion Series     Full-text available via subscription   (Followers: 6)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Croatica Chemica Acta     Open Access  
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: 18)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 64)
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  

        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  [3118 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)
       
  • Azole-hydrazone derivatives: Design, synthesis, in vitro biological
           evaluation, dual EGFR/HER2 inhibitory activity, cell cycle analysis and
           molecular docking study as anticancer agents
    • Authors: Madlen B. Labib; John N. Philoppes; Phoebe F. Lamie; Esam R. Ahmed
      Pages: 67 - 80
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Madlen B. Labib, John N. Philoppes, Phoebe F. Lamie, Esam R. Ahmed
      In this research, three series of azole-hydrazone derivatives namely, benzimidazole, benzoxazole and benzothiazole were designed and synthesized. Their structures were confirmed by elemental analysis and spectroscopic techniques. Stereochemical configuration of the synthesized compounds (Z/E) was determined. The new derivatives were tested in vitro against both human breast adenocarcinoma (MCF-7) and human hepatic adenocarcinoma (HepG2) cell lines. The most active compounds 3h (IC50 = 0.067 μM against MCF-7) and 3l (IC50 = 0.027 μM against HepG2) were further tested for Epidermal Growth Factor Receptor (EGFR) inhibitory activity. The most active 3h on EGFR was then screened for HER2 and VEGFR enzymes. Caspase-3/9 protein level expression were measured for the two compounds 3h and 3l. Cell cycle analysis showed pre G1 apoptosis and cell cycle arrest at G2/M phase. Up-regulation of Bax and down-regulation of Bcl-2 protein expression level confirmed apoptosis. Molecular docking analysis was performed for all the synthesized compounds inside the active site of EGFR.
      Graphical abstract image

      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.10.016
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis and molecular docking of thiazolidinedione based benzene
           sulphonamide derivatives containing pyrazole core as potential
           anti-diabetic agents
    • Authors: Mohd. Javed Naim; Ozair Alam; Md. Jahangir Alam; Md. Quamrul Hassan; Nadeem Siddiqui; V.G.M. Naidu; Md. Iqbal Alam
      Pages: 98 - 112
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Mohd. Javed Naim, Ozair Alam, Md. Jahangir Alam, Md. Quamrul Hassan, Nadeem Siddiqui, V.G.M. Naidu, Md. Iqbal Alam
      We herein report the design, synthesis and molecular docking studies of 2,4-thiazolidinedione derivatives containing benzene sulphonyl group which are docked against the Peroxisome Proliferator Activated Receptor (PPARγ) target. Compound 7p was most effective in lowering the blood glucose level as compared to standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR-γ transactivation of 61.2% with 1.9 folds increase in gene expression. In molecular docking studies 7p showed excellent interactions with amino acids TYR 473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not cause any damage to the liver without any noteworthy weight gain and may be considered as promising candidates for the development of new antidiabetic agents.
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      PubDate: 2017-12-26T22:43:05Z
      DOI: 10.1016/j.bioorg.2017.11.010
      Issue No: Vol. 76 (2017)
       
  • Amino acids/peptides conjugated heterocycles: A tool for the recent
           development of novel therapeutic agents
    • Authors: Meng Wang; K.P. Rakesh; Jing Leng; Wan-Yin Fang; L. Ravindar; D. Channe Gowda; Hua-Li Qin
      Pages: 113 - 129
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Meng Wang, K.P. Rakesh, Jing Leng, Wan-Yin Fang, L. Ravindar, D. Channe Gowda, Hua-Li Qin
      Amino acids/peptide conjugated heterocycles represent an important class of therapeutical agents. Biologically active heterocycles are conjugated with amino acids or peptides to increase the drug resistance. Furthermore, the amino acid/peptide based drugs have low toxicity, ample bioavailability and permeability, modest potency and good metabolic and pharmacokinetic properties. Synthetic amino acid/peptides based heterocyclic conjugates constitute a promising choice for the development of new, less toxic and safer conventional pharmaceutical drugs in the near future. In this review, we discuss and highlight the recent findings of the structural features that encourage biological applications of amino acid/peptides based conjugates.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.007
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis and evaluation of resveratrol-indazole hybrids as novel
           monoamine oxidases inhibitors with amyloid-β aggregation inhibition
    • Authors: Jin-Shuai Lan; Yun Liu; Jian-wei Hou; Jing Yang; Xin-Yu Zhang; Yuan Zhao; Sai-Sai Xie; Yue Ding; Tong Zhang
      Pages: 130 - 139
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Jin-Shuai Lan, Yun Liu, Jian-wei Hou, Jing Yang, Xin-Yu Zhang, Yuan Zhao, Sai-Sai Xie, Yue Ding, Tong Zhang
      Novel hybrids with MAO and Aβ (1–42) self-aggregation inhibitory activities were designed and synthesized with the employment of indazole moiety and resveratrol. The biological screening results indicated that most compounds displayed potent inhibitory activity for Aβ (1–42) self-aggregation, and obvious selective inhibition to MAO-B. Among these compounds, compound 6e was the most potent inhibitor not only for hMAO-B (IC50 = 1.14 μM) but also for Aβ (1–42) self-aggregation (58.9% at 20 μM). Molecular modeling and kinetic studies revealed that compound 6e was a competitive MAO-B inhibitor, which can occupy the active site of MAO-B, and interact with Aβ (1–42) via π-π and cation–π stacking interactions. In addition, compound 6e had no toxicity on PC12 cells and could cross the BBB. Collectively, all these results suggested that compound 6e might be a promising multi-target lead compound worthy of further investigation.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.009
      Issue No: Vol. 76 (2017)
       
  • Unprotected primary sulfonamide group facilitates ring-forming cascade en
           route to polycyclic [1,4]oxazepine-based carbonic anhydrase inhibitors
    • Authors: Alexander Sapegin; Stanislav Kalinin; Andrea Angeli; Claudiu T. Supuran; Mikhail Krasavin
      Pages: 140 - 146
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Alexander Sapegin, Stanislav Kalinin, Andrea Angeli, Claudiu T. Supuran, Mikhail Krasavin
      4-Chloro-3-nitrobenzenesulfonamide reacted cleanly at room-temperature with a range of bis-electrophilic phenols bearing an NH-acidic functionality (secondary carboxamide or pyrazole) in the ortho-position. This produced a novel class of [1,4]oxazepine-based primary sulfonamides which exhibited strong inhibition of therapeutically relevant human carbonic anhydrases. 2-Chloronitrobenzene did not enter a similar cyclocondensation process, even under prolonged heating. Thus, the primary sulfonamide functionality plays a dual role by enabling the [1,4]oxazepine ring construction and acting as a enzyme prosthetic zinc-binding group when the resulting [1,4]oxazepine sulfonamides are employed as carbonic anhydrase inhibitors.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.014
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis of novel Triazolones and bis-Triazolones derivatives
           under ultrasound irradiation and evaluation as potent angiotensin
           converting enzyme (ACE) inhibitors
    • Authors: Bochra Ben Salah; Salwa Hamzaoui; Fatma Krichen; Ikram Saadaoui; Riadh Ben Mansour; Nabil Miled; Ali Bougatef; Mohamed Kossentini
      Pages: 147 - 153
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Bochra Ben Salah, Salwa Hamzaoui, Fatma Krichen, Ikram Saadaoui, Riadh Ben Mansour, Nabil Miled, Ali Bougatef, Mohamed Kossentini
      The condensation of several primary amines and diamines with various N1 -ethoxycarbonyles N1 -tosylhydrazonates (1a-b), triazolones (2) and bis-triazolone (3) resulted in ethanol under ultrasound irradiation. Compared with the conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields. The newly synthesized compounds were evaluated for angiotensin I-converting enzyme (ACE) inhibition. The results were compared to Captopril as a reference drug. Compounds 3b, 2h, 3a, 2d, and 2f showed not only inhibition activity with IC50 values of 0.162, 0.253, 0.253, 0.281 and 0.382 µM, respectively, but also minimal toxicity. The docking of chemical compounds in the ACE active site showed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.004
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis and molecular modeling studies of new series of
           
    • Authors: Marwa H. El-Wakil; Hayam M. Ashour; Manal N. Saudi; Ahmed M. Hassan; Ibrahim M. Labouta
      Pages: 154 - 165
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Marwa H. El-Wakil, Hayam M. Ashour, Manal N. Saudi, Ahmed M. Hassan, Ibrahim M. Labouta
      The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives based on our lead NCI 748494/1, possessing different N-linkers to aromatic and heterocyclic rings. In addition, a molecular hybrid series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-mercaptopurine (6-MP) was synthesized in order to explore its “double-drug” antitumor effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antitumor activity. Compound 3d showed potent inhibitory activity more than reference Foretinib, BMS-777607 and NCI 748494/1 with IC50 values in the range 0.01–0.31 µM against the cancer cell lines. The calculated IC50 of 3d against c-Met kinase was found to be 2.71 µM, which is more potent than NCI 748494/1 (IC50 = 31.70 µM). Docking studies were performed to identify the binding mode of 3d with c-Met kinase domain in comparison to moderate and weak derivatives. The present study clearly demonstrates that 1,2,4-triazine ring exhibits promising antitumor activity and the double-drug optimization strategy led to identifying 3d as a potent c-Met kinase inhibitor suitable for further development.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.006
      Issue No: Vol. 76 (2017)
       
  • Modification of Bischler-Möhlau indole derivatives through palladium
           catalyzed Suzuki reaction as effective cholinesterase inhibitors, their
           kinetic and molecular docking studies
    • Authors: Shaista Parveen; Muhammad Shakil Shah; Sumera Zaib; Tayyaba Gul; Khalid Mohammed Khan; Jamshed Iqbal; Abbas Hassan
      Pages: 166 - 176
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Shaista Parveen, Muhammad Shakil Shah, Sumera Zaib, Tayyaba Gul, Khalid Mohammed Khan, Jamshed Iqbal, Abbas Hassan
      Due to the immense importance of aryl indole nucleus, herein we report the palladium-catalyzed arylation of N-substituted 2-aryl indole utilizing Suzuki-Miyaura cross coupling methodology. The biological screening for cholinesterase inhibition of the resulted biaryl indole moieties was carried out to evaluate their pharmacological potential, expecting to involve the development of new therapeutics for various inflammatory, cardiovascular, gastrointestinal and neurological diseases. This research work also involved the use of utilization of microwave-assisted organic synthesis (MAOS) for the synthesis of Bischler-Möhlau indole which is further biarylated via palladium-catalyzed cross coupling reaction. All the synthetic compounds (3a-n) were tested for cholinesterase inhibition and exhibited high level of AChE inhibitory activities. Interestingly, compounds 3m and 3n were found to be dual inhibitors, however, remaining compound exhibited no inhibitory activity against BChE. The biological potential of the resulted compounds was explained on the basis of molecular docking studies, performed against AChE and BChE, exploring the probable binding modes of most potent inhibitors.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.003
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis, monoamine oxidase inhibition and docking studies of new
           dithiocarbamate derivatives bearing benzylamine moiety
    • Authors: Betül Kaya Çavuşoğlu; Begüm Nurpelin Sağlık; Yusuf Özkay; Beril İnci; Zafer Asım Kaplancıklı
      Pages: 177 - 187
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Yusuf Özkay, Beril İnci, Zafer Asım Kaplancıklı
      A new series of thirteen 2-[(4-fluorophenyl)(4-nitrobenzyl)amino]-2-oxoethyl-1-substituted-carbodithioate derivatives (4a-4m) were synthesized and tested for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory potential by an in vitro fluorometric method. Most of the compounds have found to be selective towards MAO-B than MAO-A. Compound 4j that carrying 4-nitrophenyl piperazine moiety, was detected as the most active agent amongst all compounds with the IC50 value of 0.097 ± 0.003 µM for MAO-B while that of selegiline was 0.040 ± 0.002 µM. The enzyme kinetic study reported that compound 4j is a reversible and non-competitive inhibitor. Interaction modes between the hMAO-B and compound 4j were determined by docking studies. The study also revealed that compound 4j has the highest binding scores. Besides, compound 4j has not cytotoxicity at its effective concentration against hMAO-B.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.012
      Issue No: Vol. 76 (2017)
       
  • The “Janus face” of the thrombin binding aptamer: Investigating the
           anticoagulant and antiproliferative properties through straightforward
           chemical modifications
    • Authors: Veronica Esposito; Annapina Russo; Teresa Amato; Valentina Vellecco; Mariarosaria Bucci; Luciano Mayol; Giulia Russo; Antonella Virgilio; Aldo Galeone
      Pages: 202 - 209
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Veronica Esposito, Annapina Russo, Teresa Amato, Valentina Vellecco, Mariarosaria Bucci, Luciano Mayol, Giulia Russo, Antonella Virgilio, Aldo Galeone
      Background The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Methods Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5′-GGTTGGTGTGGTTGG-3′) and containing 2′-deoxyuridine (U) or 5-bromo-2′-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2′-deoxyuridine (H) residues in the same positions, previously investigated. Results The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. Conclusions All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. General significance: The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.005
      Issue No: Vol. 76 (2017)
       
  • Synthesis and biological evaluation of new oxopyrrolidine derivatives as
           inhibitors of acetyl cholinesterase and β amyloid protein as anti –
           Alzheimer’s agents
    • Authors: Lamia W. Mohamed; Suzan M. Abuel-Maaty; Waleed A. Mohammed; May A. Galal
      Pages: 210 - 217
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Lamia W. Mohamed, Suzan M. Abuel-Maaty, Waleed A. Mohammed, May A. Galal
      A new series of oxopyrrolidines was synthesized and evaluated for their effect on Alzheimer‘s disease by measuring their inhibitory activity against acetyl cholinesterase enzyme and amyloid β 42 protein. Most of the compounds showed good inhibitory activity with ethyl 2-(2-(2, 6-dimethylphenylcarbamoyl)- 5-oxopyrrolidin-1-yl) acetate (V) having the highest activity against acetyl cholinesterase with IC50 value 1.84 ng/g tissue compared to standard donepezil 3.34 ng/g tissue. Furthermore, compound 1-((4-(4-chlorophenyl) piperazin-1-yl) methyl)-N-(2,6-dimethylphenyl)-5- oxopyrrolidine- 2-carboxamide (IIIe) displayed the highest activity against β 42 protein with IC50 value of 11.3 Pg/g tissue compared to 18.4 Pg/g tissue of donepezil.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.008
      Issue No: Vol. 76 (2017)
       
  • Sulfonamides containing curcumin scaffold: Synthesis, characterization,
           carbonic anhydrase inhibition and molecular docking studies
    • Authors: Mahmood Ahmed; Muhammad Abdul Qadir; Abdul Hameed; Muhammad Nadeem Arshad; Abdullah M. Asiri; Muhammad Muddassar
      Pages: 218 - 227
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Mahmood Ahmed, Muhammad Abdul Qadir, Abdul Hameed, Muhammad Nadeem Arshad, Abdullah M. Asiri, Muhammad Muddassar
      Curcumin is a multi-functional pharmacologically safe natural agent with proven cytoprotective effects to healthy human cells. In this study, a new series of sulfonamides with curcumin scaffold were synthesized, characterized and investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine) isoforms. The structures of newly synthesized compounds were described by IR, 1H NMR and 13C NMR spectral data. Compound 14 showed the Ki value of 0.99 µM with highest inhibitory activity among all other synthesized compounds against hCA-I enzyme. Similarly enzyme kinetic studies of compound 14, 16 and 30 against bCAII enzyme showed Ki values of 0.71, 0.67 and 0.71 µM respectively. Our biological assays results showed that most of active compounds have similar inhibitory activities compared to standard acetazolamide drug. The molecular docking predicted binding modes showed that these compounds bind with hCA-1 enzyme in similar fashion.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.015
      Issue No: Vol. 76 (2017)
       
  • Synthesis of derivatives of cleistopholine and their
           anti-acetylcholinesterase and anti-β-amyloid aggregation activity
    • Authors: Zhenhua Wu; Wenxia Liao; Kelin Chen; Jingfang Qin; Huang Tang
      Pages: 228 - 236
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Zhenhua Wu, Wenxia Liao, Kelin Chen, Jingfang Qin, Huang Tang
      A series of 6- and 9-substituted cleistopholine derivatives has been designed, synthesized and investigated to inhibit the aggregation of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-myloid (A β). Results showed that these synthetic compounds had excellent AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced A β aggregation. When SH-SY5Y cells were treated with these substituted cleistopholine derivatives during they overexpressed the Swedish mutant form of human β -amyloid precursor protein (APPsw), A β 42 secretion levels were significantly reduced. According to a parallel artificial membrane permeation assay for BBB, seven out of these sixteen synthetic compounds probably could cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS).
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.011
      Issue No: Vol. 76 (2017)
       
  • 4-Aminopyridine based amide derivatives as dual inhibitors of tissue
           non-specific alkaline phosphatase and ecto-5′-nucleotidase with
           potential anticancer activity
    • Authors: Sidra Hassan; Syeda Abida Ejaz; Aamer Saeed; Muddasar Shehzad; Shafi Ullah Khan; Joanna Lecka; Jean Sévigny; Ghulam Shabir; Jamshed Iqbal
      Pages: 237 - 248
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Sidra Hassan, Syeda Abida Ejaz, Aamer Saeed, Muddasar Shehzad, Shafi Ullah Khan, Joanna Lecka, Jean Sévigny, Ghulam Shabir, Jamshed Iqbal
      Ecto-nucleotidase members i.e., ecto-5′-nucleotidase and alkaline phosphatase, hydrolyze extracellular nucleotides and play an important role in purinergic signaling. Their overexpression are implicated in a variety of pathological states, including immunological diseases, bone mineralization, vascular calcification and cancer, and thus they represent an emerging drug targets. In order to design potent and selective inhibitors, new derivatives of 4-aminopyridine have been synthesized (10a-10m) and their structures were established on the basis of spectral data. The effect of nature and position of substituent was interestingly observed and justified on the basis of their detailed structure activity relationships (SARs) against both families of ecto-nucleotidase. Compound 10a displayed significant inhibition (IC50 ± SEM = 0.25 ± 0.05 µM) that was found ≈168 fold more potent as compared to previously reported inhibitor suramin (IC50 ± SEM = 42.1 ± 7.8 µM). This compound exhibited 6 times more selectivity towards h-TNAP over h-e5′NT. The anticancer potential and mechanism were also established using cell viability assay, flow cytometric analysis and nuclear staining. Molecular docking studies were also carried out to gain insight into the binding interaction of potent compounds within the respective enzyme pockets and herring-sperm DNA.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.013
      Issue No: Vol. 76 (2017)
       
  • Synthesis, biological evaluation and molecular docking studies of a new
           series of chalcones containing naphthalene moiety as anticancer agents
    • Authors: Guangcheng Wang; Jie Qiu; Xiangwei Xiao; Anbai Cao; Fengjiao Zhou
      Pages: 249 - 257
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Guangcheng Wang, Jie Qiu, Xiangwei Xiao, Anbai Cao, Fengjiao Zhou
      A series of chalcones containing naphthalene moiety 4a–4p have been synthesized, characterized by 1H NMR and 13C NMR and evaluated for their in vitro anticancer activity. The majority of the screened compounds displayed potent anticancer activity against both HCT116 and HepG2 human cancer cell lines. Among the series, compound 4h with a diethylamino group at the para position of the phenyl ring exhibited the most potent anticancer activity against HCT116 and HepG2 cell lines with IC50 values of 1.20 ± 0.07 and 1.02 ± 0.04 μM, respectively. The preliminary structure–activity relationship has been summarized. Tubulin polymerization experiments indicated that 4h effectively inhibited tubulin polymerization and flow cytometric assay revealed that 4h arrests HepG2 cells at the G2/M phase in a dose-dependent manner. Furthermore, molecular docking studies suggested that 4h binds to the colchicine binding site of tubulin.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.017
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis and evaluation of novel
           N-hydroxybenzamides/N-hydroxypropenamides incorporating
           quinazolin-4(3H)-ones as histone deacetylase inhibitors and antitumor
           agents
    • Authors: Doan Thanh Hieu; Duong Tien Anh; Nguyen Minh Tuan; Pham-The Hai; Le-Thi-Thu Huong; Jisung Kim; Jong Soon Kang; Tran Khac Vu; Phan Thi Phuong Dung; Sang-Bae Han; Nguyen-Hai Nam; Nguyen-Dang Hoa
      Pages: 258 - 267
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Doan Thanh Hieu, Duong Tien Anh, Nguyen Minh Tuan, Pham-The Hai, Le-Thi-Thu Huong, Jisung Kim, Jong Soon Kang, Tran Khac Vu, Phan Thi Phuong Dung, Sang-Bae Han, Nguyen-Hai Nam, Nguyen-Dang Hoa
      In our search for novel small molecules targeting histone deacetylases, we have designed and synthesized several series of novel N-hydroxybenzamides/N-hydroxypropenamides incorporating quinazolin-4(3H)-ones (4a-h, 8a-d, 10a-d). Biological evaluation showed that these hydroxamic acids were generally cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). It was found that the N-hydroxypropenamides (10a-d) were the most potent, both in term of HDAC inhibition and cytotoxicity. Several compounds, e.g. 4e, 8b-c, and 10a-c, displayed up to 4-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in term of cytotoxicity. These compounds also comparably inhibited HDACs with IC50 values in sub-micromolar range. Docking experiments on HDAC2 isozyme revealed some important features contributing to the inhibitory activity of synthesized compounds, especially for propenamide analogues. Importantly, the free binding energy computed was found to have high quantitative correlation (R 2 ∼ 95%) with experimental results.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.007
      Issue No: Vol. 76 (2017)
       
  • First evaluation of organotellurium derivatives as carbonic anhydrase I,
           II, IV, VII and IX inhibitors
    • Authors: Andrea Angeli; Damiano Tanini; Antonella Capperucci; Claudiu T. Supuran
      Pages: 268 - 272
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Andrea Angeli, Damiano Tanini, Antonella Capperucci, Claudiu T. Supuran
      A series of tellurides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) carbonic anhydrase isoforms hCA I, II, IV, VII and IX, involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. These compounds, which are the first tellurium-containing derivatives acting as inhibitors of carbonic anhydrase enzymes, showed effective inhibition against all isoforms investigated and some of them were selective for inhibiting the cytosolic or the membrane-bound CAs. Thus, these carbonic anhydrase inhibitors are interesting leads for the development of isoform-selective inhibitors.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.010
      Issue No: Vol. 76 (2017)
       
  • Design, synthesis, and initial evaluation of affinity-based small
           molecular probe for detection of WDR5
    • Authors: Wei-Lin Chen; Dong-Dong Li; Zhi-Hui Wang; Xiao-Li Xu; Xiao-Jin Zhang; Zheng-Yu Jiang; Xiao-Ke Guo; Qi-Dong You
      Pages: 380 - 385
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Wei-Lin Chen, Dong-Dong Li, Zhi-Hui Wang, Xiao-Li Xu, Xiao-Jin Zhang, Zheng-Yu Jiang, Xiao-Ke Guo, Qi-Dong You
      WDR5, a subunit of the SET/MLL complex, plays critical roles in various biological progresses and are abnormally expressed in many cancers. Here we report the design, synthesis, and biochemical characterization of a new chemical tool to capture WDR5 protein. The probe is a biotinylated version of compound 30 that is a potent WDR5 inhibitor we previously reported. Importantly, the probe displayed high affinity to WDR5 protein in vitro binding potency and showed the ability in specifically and real time monitoring WDR5 protein. Further, the biotinylated tag of the probe enabled selectively “chemoprecipitation” of WDR5 from whole cell lysates of MV4-11. This probe provided a new approach to identify the overexpressed WDR5 protein in different cancer cells and applications to proteomic analysis of WDR5 and WDR5-binding partners.
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      PubDate: 2017-12-26T22:43:05Z
      DOI: 10.1016/j.bioorg.2017.11.018
      Issue No: Vol. 76 (2017)
       
  • A simple and efficient synthesis of benzimidazoles containing piperazine
           or morpholine skeleton at C-6 position as glucosidase inhibitors with
           antioxidant activity
    • Authors: Musa Özil; Cansu Parlak; Nimet Baltaş
      Pages: 468 - 477
      Abstract: Publication date: February 2018
      Source:Bioorganic Chemistry, Volume 76
      Author(s): Musa Özil, Cansu Parlak, Nimet Baltaş
      A novel 2-(aryl)-6-morpholin-4-yl(or 4-methylpiperazin-1-yl)-1H-benzimidazole derivatives were designed and expeditiously synthesized starting from 5-morpholin-4-yl(or 4-methylpiperazin-1-yl)-2-nitroaniline with various aldehydes which were preliminarily screened for in vitro antioxidant activities and glucosidase inhibitors. The benzimidazoles were effectively synthesized by a rapid ‘onepot’ nitro reductive cyclization reaction using sodium hydrosulfite as a reagent. All reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. Antioxidant activities of the synthesized compounds were clarified using various in vitro antioxidant assays including Cupric Reducing Antioxidant Capacity (CUPRAC, ranging from 5.511 to 19.703 mM Trolox/mg compound) and Ferric Reducing Antioxidant Power (FRAP) (1.141–12.943 mM FeSO4·7H2O/mg compound) assays. Also, the radical scavenging activities of these compounds were assayed using ABTS + and DPPH methods. The results showed that all compounds exhibited very high scavenging activity. These synthesized compounds were then evaluated for their α-glucosidase inhibitory potential and seven compounds demonstrated an inhibitory potential much better than the standard acarbose. Herein, we will provide details of the structure activity relationship of the benzimidazole analog for the potency.
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      PubDate: 2017-12-26T22:43:05Z
      DOI: 10.1016/j.bioorg.2017.12.019
      Issue No: Vol. 76 (2017)
       
  • Design and Synthesis of Cell Selective α/β-Diastereomeric Peptidomimetic
           with Potent In vivo Antibacterial Activity against Methicillin Resistant
           S. aureus
    • Authors: Rikeshwer Prasad Dewangan; Gopal Singh Bisht; Vijay Pal Singh; Mohammad Shahar Yar; Santosh Pasha
      Abstract: Publication date: Available online 26 December 2017
      Source:Bioorganic Chemistry
      Author(s): Rikeshwer Prasad Dewangan, Gopal Singh Bisht, Vijay Pal Singh, Mohammad Shahar Yar, Santosh Pasha
      Design of therapeutically viable antimicrobial peptides with cell selectivity against microorganisms is an important step towards the development of new antimicrobial agents. Here, we report four de novo designed, short amphipathic sequences based on a α-helical template comprising of Lys, Trp and Leu or their corresponding D-and/or β- amino acids. Sequence A-12 was protease susceptible whereas its α/β-diastereomeric analogue UNA-12 was resistant to trypsin and proteinase K up to 24 h. A-12 and UNA-12 exhibited broad-spectrum antibacterial activity (MIC: 2-32 µg/mL) against pathogens including methicillin resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). Interestingly, A-12 was found to be most toxic (>50% haemolytic at 250 µg/mL) whereas UNA-12 was found to be non cytotoxic among the all analogues against hRBCs and human keratinocytes. Interaction studies with artificial membranes by tryptophan fluorescence and acrylamide quenching assay demonstrated A-12 interacted equally in bacterial as well as mammalian mimic membrane whereas UNA-12 was found to be more selective towards bacterial mimic membrane. Further microscopic tool has revealed membrane damaging ability of A-12 and UNA-12 with bactericidal mode of action against MRSA. Encouragingly, peptidomimetics analogue UNA-12 showed remarkable safety and efficacy against MRSA in in-vivo neutropenic mice thigh infection model. In summary, simultaneous replacement of the natural amino acids with D-/β- congeners is a promising strategy for designing of potent, cell selective and protease stable peptide based antibiotics.
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      PubDate: 2017-12-26T22:43:05Z
      DOI: 10.1016/j.bioorg.2017.12.020
       
  • Design and synthesis of tumor-targeting theranostic drug conjugates for
           SPECT and PET imaging studies
    • Authors: Tao Wang; Jacob G. Vineberg; Tadashi Honda; Iwao Ojima
      Abstract: Publication date: Available online 11 December 2017
      Source:Bioorganic Chemistry
      Author(s): Tao Wang, Jacob G. Vineberg, Tadashi Honda, Iwao Ojima
      Theranostics will play a significant role in the next generation chemotherapy. Two novel tumor-targeting theranostic drug conjugates, bearing imaging arms, were designed and synthesized. These theranostic conjugates consist of biotin as the tumor-targeting moiety, a second generation taxoid, SB-T-1214, as a potent anticancer drug, and two different imaging arms for capturing 99mTc for SPECT (single photon emission computed tomography) and 64Cu for PET (positron emission tomography). To explore the best reaction conditions for capturing radionuclides and work out the chemistry directly applicable to “hot” nucleids, cold chemistry was investigated to capture 185Re(I) and 63Cu(II) species as surrogates for 99mTc and 64Cu, respectively.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.018
       
  • Aminoadamantanes Containing Monoterpene-derived Fragments as Potent
           Tyrosyl-DNA phosphodiesterase 1 Inhibitors
    • Authors: Konstantin Yu. Ponomarev; Evgeniy V. Suslov; Alexandra L. Zakharenko; Olga D. Zakharova; Artem D. Rogachev; Dina V. Korchagina; Ayesha Zafar; Jóhannes Reynisson; Andrey A. Nefedov; Konstantin P. Volcho; Nariman F. Salakhutdinov; Olga I. Lavrik
      Abstract: Publication date: Available online 9 December 2017
      Source:Bioorganic Chemistry
      Author(s): Konstantin Yu. Ponomarev, Evgeniy V. Suslov, Alexandra L. Zakharenko, Olga D. Zakharova, Artem D. Rogachev, Dina V. Korchagina, Ayesha Zafar, Jóhannes Reynisson, Andrey A. Nefedov, Konstantin P. Volcho, Nariman F. Salakhutdinov, Olga I. Lavrik
      The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.005
       
  • Bioactivity evaluation of natural product α-mangostin as a novel
           xanthone-based lysine-specific demethylase 1 inhibitor to against tumor
           metastasis
    • Authors: Chao Han; Zhongrui Li; Jiqin Hou; Zhen Wang; Dingqiao Xu; Guimin Xue; Lingyi Kong
      Abstract: Publication date: Available online 8 December 2017
      Source:Bioorganic Chemistry
      Author(s): Chao Han, Zhongrui Li, Jiqin Hou, Zhen Wang, Dingqiao Xu, Guimin Xue, Lingyi Kong
      Lysine-specific demethylase 1 (LSD1), which has been reported to be overexpressed in several human cancers, has recently emerged as an attractive therapeutic target for treating cancer. To date, almost all the developed LSD1 inhibitors are chemo-synthesized molecules, while α-mangostin is first characterized as xanthone-based natural inhibitor in the current study with IC50 values of 2.81±0.44 μM. Bioactivity study and docking analysis indicated that α-mangostin could inhibit MDA-MB-231 cells migration and evasion through inhibit intracellular LSD1 activity. These findings provides new molecular skeleton for LSD1 inhibitor study and should encourage further modification of α-mangostin to produce more potent LSD1 inhibitors with potential anticancer activity.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.004
       
  • Synthesis of Imidazo-thiadiazole linked Indolinone Conjugates and
           evaluated their Microtubule network disrupting and Apoptosis Inducing
           ability
    • Authors: M.P. Narasimha Rao; Burri. Nagaraju; Jeshma Kovvuri; Sowjanya Polepalli; Sateesh Alavala; M.V.P.S. Vishnuvardhan; P. Swapna; Vijaykumar D. Nimbarte; Jerripothula K. Lakshmi; Nishant Jain; Ahmed Kamal
      Abstract: Publication date: Available online 7 December 2017
      Source:Bioorganic Chemistry
      Author(s): M.P. Narasimha Rao, Burri. Nagaraju, Jeshma Kovvuri, Sowjanya Polepalli, Sateesh Alavala, M.V.P.S. Vishnuvardhan, P. Swapna, Vijaykumar D. Nimbarte, Jerripothula K. Lakshmi, Nishant Jain, Ahmed Kamal
      A series of imidazo[2,1-b][1,3,4]thiadiazole linked indolinone conjugates were synthesized and investigated for antiproliferative activity in different human cancer cell lines by changing various substitutions at indolinone and phenyl ring systems. Among them conjugates 7, 14 and 15 were exhibited potent antiproliferative activity with GI50 values from 0.13-3.8 μΜ and evaluated for cell cycle analysis, tubulin polymerization assay and apoptosis. Treatment with 7, 14 and 15 were resulted in accumulation of cells in G2/M phase, inhibition of tubulin assembly, disruption of microtubule network. Inhibition of tubulin polymerization was further supported by Western blot analysis. In addition, the conjugates (7, 14 and 15) also showed apoptosis in HeLa cell line, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase-3 assays suggested that these compounds induce cell death by apoptosis. Docking studies revealed that these compounds (7, 14 and 15) bind with αAsn101, αThr179, αSer178, βCys241, βLys254 and βLys352 in the colchicine-binding site of the tubulin.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.021
       
  • Bioactive polyoxygenated seco-cyclohexenes from Artabotrys hongkongensis
    • Authors: Yan-Ping Liu; Jin-Ying Tang; Yan Hua; Liang Lai; Xiu-Lan Luo; Zhi-Jie Zhang; Wen-Qing Yin; Guang-Ying Chen; Yan-Hui Fu
      Abstract: Publication date: Available online 7 December 2017
      Source:Bioorganic Chemistry
      Author(s): Yan-Ping Liu, Jin-Ying Tang, Yan Hua, Liang Lai, Xiu-Lan Luo, Zhi-Jie Zhang, Wen-Qing Yin, Guang-Ying Chen, Yan-Hui Fu
      Six new polyoxygenated seco-cyclohexenes, artahongkongenes A-F (1-6), together with six known analogues (7-12) were isolated from the stems and leaves of Artabotrys hongkongensis. Their structures were elucidated by extensive spectroscopic methods. All new compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. New seco-cyclohexenes 1-6 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.26 to 16.58 μM.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.011
       
  • Design, Synthesis, and Biological Evaluation of Deuterated Phenylpropionic
           Acid Derivatives as Potent and Long-Acting Free Fatty Acid Receptor 1
           Agonists
    • Authors: Zheng Li; Chunxia Liu; Xue Xu; Wei Shi; Huilan Li; Yuxuan Dai; Xingguang Cai; Wenlong Huang; Hai Qian
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Zheng Li, Chunxia Liu, Xue Xu, Wei Shi, Huilan Li, Yuxuan Dai, Xingguang Cai, Wenlong Huang, Hai Qian
      The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancement of glucose-stimulated insulin secretion. Takeda’s compound 1 has robustly in vitro activity for FFA1, but it has been suffered from poor pharmacokinetic (PK) profiles because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available agonists, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid. Interestingly, the differences of physicochemical properties between hydrogen and deuterium are quite small, but there are many differences in the structure-activity relationship between phenylpropionic acid series and present deuterated series. Further optimizations of deuterated series led to the discovery of compound 18, which exhibited a superior balance in terms of in vitro activity, lipophilicity, and solubility. Better still, compound 18 revealed a lower clearance (CL = 0.44 L/h/kg), higher maximum concentration (C max = 7584.27 μg/L), and longer half-life (T 1/2 = 4.16 h), resulting in a > 23-fold exposure than compound 1. In subsequent in vivo pharmacodynamic studies, compound 18 showed a robustly glucose-lowering effect in rodent without the risk of hypoglycemia.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.012
       
  • Design, Synthesis, Antibacterial Evaluation and Molecular Docking Studies
           of Some New Quinoxaline Derivatives Targeting Dihyropteroate Synthase
           Enzyme
    • Authors: Maryam A.Z. El-Attar; Omaima G. Shaaban; Rasha Y. Elbayaa; Nargues S. Habib; Abeer E. Abdel Wahab; Ibrahim A. Abdelwahab; Soad A.M. El-Hawash
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Maryam A.Z. El-Attar, Omaima G. Shaaban, Rasha Y. Elbayaa, Nargues S. Habib, Abeer E. Abdel Wahab, Ibrahim A. Abdelwahab, Soad A.M. El-Hawash
      Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. From this perspective, new quinoxaline derivatives bearing various bioactive heterocyclic moieties (thiadiazoles, oxadiazoles, pyrazoles and thiazoles) were designed and synthesized. The newly synthesized compounds were evaluated for their in-vitro antibacterial activity against nine bacterial human pathogenic strains using the disc diffusion assay. In general, most of the synthesized compounds exhibited good antibacterial activities. The thiazolyl 11c displayed significant antibacterial activities against P. aeruginosa (MIC, 12.5 µg/mL vs levofloxacin 12.5µg/mL).Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of bacterial DHPS enzyme. The results provide important information for the future design of more potent antibacterial agents.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.017
       
  • NO inhibitory constituents as potential anti-neuroinflammatory agents for
           AD from Blumea balsamifera
    • Authors: Jun Ma; Quanhui Ren; Bangjian Dong; Zhaoyu Shi; Jie Zhang; Da-Qing Jin; Jing Xu; Yasushi Ohizumi; Dongho Lee; Yuanqiang Guo
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Jun Ma, Quanhui Ren, Bangjian Dong, Zhaoyu Shi, Jie Zhang, Da-Qing Jin, Jing Xu, Yasushi Ohizumi, Dongho Lee, Yuanqiang Guo
      Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of one new labdane diterpenoid and three new guaiane sesquiterpenoids, as well as ten known compounds from Blumea balsamifera. Their structures were elucidated by NMR spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The anti-neuroinflammatory effects were examined by inhibiting NO release in 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 iNOS protein.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.008
       
  • Novel 1,2,4-triazole derivatives as potential anticanceragents: Design,
           synthesis, molecular docking and mechanistic studies
    • Authors: Hany A.M. El-Sherief; Bahaa G.M. Youssif; Syed Nasir Abbas Bukhari; Mohamed Abdel-Aziz; Hamdy M. Abdel-Rahman
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Hany A.M. El-Sherief, Bahaa G.M. Youssif, Syed Nasir Abbas Bukhari, Mohamed Abdel-Aziz, Hamdy M. Abdel-Rahman
      A series of novel compounds carrying 1,2,4-triazole scaffold was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines using MTT assay. Compounds 8a, 8b, 8c, 8d, 10b, 10e, and 10g showed remarkable antiproliferative activity against the tested cell lines. Compounds 8a, 8b, 8c, 8d, 10b, 10e, and 10g with the least IC50 values in MTT assay were tested against three known anticancer targets including EGFR, BRAF and Tubulin. The results revealed that compounds 8c and 8d showed almost same BRAF inhibitory activity and were discovered to be potent inhibitors of cancer cell proliferation and were also observed to be strong Tubulin inhibitors. Moreover, 8c also showed the best EGFR inhibition with IC50 = 3.6 μM. Finally molecular modeling studies were performed to explore the binding mode of the most active compounds to the target enzymes.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.013
       
  • Development of Optimized Conditions for Glaser-Hay Bioconjugations
    • Authors: Zachary M. Nimmo; John F. Halonski; Lindsay E. Chatkewitz; Douglas D. Young
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Zachary M. Nimmo, John F. Halonski, Lindsay E. Chatkewitz, Douglas D. Young
      The efficient preparation of protein bioconjugates represents a route to novel materials, diagnostics, and therapeutics. We previously reported a novel bioorthogonal Glaser-Hay reaction for the preparation of covalent linkages between proteins and a reaction parner; however, deleterious protein degradation was observed under extended reaction conditions. Herein, we describe the systematic optimization of the reaction to increase coupling efficiency and decrease protein degradation. Two optimized condtions were identified varying either the pH of the reaction or the bidentate ligand employed, allowing for more rapid conjugations and/or less protein oxidation.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.020
       
  • Protonography and anion inhibition profile of the α-carbonic anhydrase
           (CruCA4) identified in the Mediterranean red coral Corallium rubrum
    • Authors: Sonia Del Prete; Daniela Vullo; Natacha Caminiti-Segonds; Didier Zoccola; Sylvie Tambutté; Claudiu T. Supuran; Clemente Capasso
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Sonia Del Prete, Daniela Vullo, Natacha Caminiti-Segonds, Didier Zoccola, Sylvie Tambutté, Claudiu T. Supuran, Clemente Capasso
      CruCA4 is a secreted isoform of the α-carbonic anhydrase (CA, EC 4.2.1.1) family, which has been identified in the octocoral Corallium rubrum. This enzyme is involved in the calcification process leading to the formation of the coral calcium carbonate skeleton. We report here experiments performed on the recombinant CruCA4 with the technique of protonography that can be used to detect in a simple way the enzyme activity. We have also investigated the inhibition profile of CruCA4 with one major class of CA inhibitors, the inorganic anions. A range of weak and moderate inhibitors have been identified having KI in the range of 1-100 mM, among which the halides, pseudohalides, bicarbonate, sulfate, nitrate, nitrite, and many complex inorganic anions. Stronger inhibitors were sulfamide, sulfamate, phenylboronic acid, phenylarsonic acid, and diethylditiocarbamate, which showed a better affinity for this enzyme, with KI in the range of 75 μM – 0.60 mM. All these anions/small molecules probably coordinate to the Zn(II) ion within the CA active site as enzyme inhibition mechanism.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.009
       
  • Carbazole alkaloids from Clausena hainanensis with their potential
           antiproliferative activities
    • Authors: Yan-Lei Ma; Yan-Ping Liu; Chao Zhang; Wan-Hui Zhao; Shi Shi; Dan-Nv He; Pan Zhang; Xiao-Hong Liu; Ting-Ting Han; Yan-Hui Fu
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Yan-Lei Ma, Yan-Ping Liu, Chao Zhang, Wan-Hui Zhao, Shi Shi, Dan-Nv He, Pan Zhang, Xiao-Hong Liu, Ting-Ting Han, Yan-Hui Fu
      Five new carbazole alkaloids, clausehainanines A-E (1-5), together with seven known analogues (6-12) were isolated from the stems and leaves of C. hainanensis. Their structures were elucidated by extensive spectroscopic methods. Among them, compounds 1-5 were an unusual type of carbazole alkaloids, possessing diverse isopentenyl derivatives as substituents at C-2. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Alkaloids 1-12 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.12 to 15.56 μM. These findings suggest that the discoveries of these carbazole alkaloids with significant cytotoxic activities isolated from C. hainanensis could be of great importance to the development of new anticancer agents.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.016
       
  • Biological evaluation of New imidazole derivatives tethered with indole
           moiety as Potent α-Glucosidase Inhibitors
    • Authors: Sadia Naureen; Faryal Chaudhry; Munawar Ali Munawar; Muhammad Ashraf; Sujhla Hamid; MisbahulAin Khan
      Abstract: Publication date: Available online 5 December 2017
      Source:Bioorganic Chemistry
      Author(s): Sadia Naureen, Faryal Chaudhry, Munawar Ali Munawar, Muhammad Ashraf, Sujhla Hamid, MisbahulAin Khan
      A series of triarylimidazoles substituted with 2-arylindoles (4a-4j) were prepared and evaluated for their in vitro α-Glucosidase inhibition. α-Glucosidase inhibition assay displayed a new class of highly potent agents The new compounds showed significant α-glucosidase inhibitory activity as compared to the standard inhibitor acrabose. Structures of synthesized compounds were determined by using Mass spectrometry FT-IR,1H NMR and 13C NMR.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.014
       
  • Design, Synthesis, Molecular Docking of New Lipophilic Acetamide
           Derivatives Affording Potential Anticancer and Antimicrobial Agents
    • Authors: Hany E.A. Ahmed; Saleh K. Ihmaid; Abdelsattar M. Omar; A.M. Shehata; Heba S. Rateb; Mohammed F. Zayed; Sahar Ahmed; Mahmoud M. Elaasser
      Abstract: Publication date: Available online 2 December 2017
      Source:Bioorganic Chemistry
      Author(s): Hany E.A. Ahmed, Saleh K. Ihmaid, Abdelsattar M. Omar, A.M. Shehata, Heba S. Rateb, Mohammed F. Zayed, Sahar Ahmed, Mahmoud M. Elaasser
      Fifteen new substituted N-2-(2-oxo-3-phenylquinoxalin-1(2H)-yl) acetamides 5a-f, 6a-f, and 8a-c were synthesized by reacting ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate with various primary amines including benzylamines, sulfonamides, and amino acids. The in vitro antimicrobial screening of the target compounds was screened to assess their antibacterial and antifungal activity. As a result, seven compounds namely; 5a, 5c, 5d, 6a, 6c, 8b and 8c showed a promising broad spectrum antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the analogs 5c and 6d were nearly as equiactive as ciprofloxacin drug. Meanwhile, four compounds namely; 5c, 6a, 6f and 8c exhibited appreciable antifungal activity with MIC values range 33-40 mg/mL comparable with clotrimazole (MIC 25 mg/mL). In addition, the anticancer effects of the synthesized compounds were evaluated against three cancer lines. The data obtained revealed the benzylamines and sulpha derivatives were the most active compounds especially 5f and 6f ones. Further EGFR enzymatic investigation was carried out for these most active compounds 5f and 6f resulting in inhibitory activity by 1.89 and 2.05 µM respectively. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds toward the enzyme target, EGFR protein kinase enzyme. The results revealed good compounds placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Collectively, the analogs 5f and 6fcould be further utilized and optimized as good cytotoxic agents.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.11.019
       
  • Oxindole based oxadiazole hybrid analogs: Novel α-glucosidase
           inhibitors
    • Authors: Muhammad Taha; Syahrul Imran; Fazal Rahim; Abdul Wadood; Khalid Mohammed Khan
      Abstract: Publication date: Available online 2 December 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Syahrul Imran, Fazal Rahim, Abdul Wadood, Khalid Mohammed Khan
      Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. Beside these α-glucosidase inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in view the greater importance of α-glucosidase inhibitors here in this study we are presenting oxindole based oxadiazoles hybrid analogs (1–20) synthesis, characterized by different spectroscopic techniques including 1H-NMR and EI-MS and their α-glucosidase inhibitory activity. All compounds were found potent inhibitors for the enzyme with IC50 values ranging between 1.25 ± 0.05 to 268.36±4.22µM when compared with the standard drug acarbose having IC50 value 895.09 ± 2.04µM. Our study identifies novel series of potent α-glucosidase inhibitors and further investigation on this may led to the lead compounds. A structure activity relationship has been established for all compounds. The interactions of the active compounds and enzyme active site were established with the help of molecular docking studies.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.001
       
  • Synthesis, anti-inflammatory, p38α MAP kinase inhibitory activities and
           molecular docking studies of quinoxaline derivatives containing triazole
           moiety
    • Authors: Sana Tariq; Ozair Alam; Mohd. Amir
      Abstract: Publication date: Available online 2 December 2017
      Source:Bioorganic Chemistry
      Author(s): Sana Tariq, Ozair Alam, Mohd. Amir
      A new series of 3-[2-(5-mercapto-4-phenyl-4H-1,2,4-traiazol-3-yl)ethyl] quinoxalin-2(1H)-one (5a-v) derivatives was synthesized and subjected to in vitro evaluation for anti-inflammatory activity (BSA anti-denaturation assay) and p38α MAPK inhibition. Few selected compounds (5a, 5e, 5f, 5g, 5h, 5l, 5q and 5u) were studied for their in vivo anti-inflammatory activity, ulcerogenicity and lipid peroxidation potential. Compounds 5e and 5f were found to be the most active in the series showing 83.45% and 84.15% anti-inflammatory activity respectively when compared to diclofenac sodium (83.22%). They were also found to have low ulcerogenic potential and lipid peroxidation. The p38α MAP kinase inhibition of the compounds 5e and 5f was also found to be slightly better than the standard SB 203580. The compounds were also docked against p38α MAP kinase enzyme in order to predict their binding mode. Compounds 5e and 5f showed stronger binding with an additional hydrogen bond interaction with ASP-168 which was not observed in SB 203580.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.003
       
  • Pharmacokinetic studies of naproxen amides of some amino acid esters with
           promising colorectal cancer chemopreventive activity
    • Authors: Tarek Aboul-Fadl; Soliman A. Al-Hamad; Ehab A. Fouad
      Abstract: Publication date: Available online 2 December 2017
      Source:Bioorganic Chemistry
      Author(s): Tarek Aboul-Fadl, Soliman A. Al-Hamad, Ehab A. Fouad
      Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported. Those prodrugs showed a promising colorectal cancer chemopreventive activity. The current study aims to investigate the fate and hydrolysis of the prodrugs kinetically in different pH conditions, simulated gastric and intestinal fluids with pHs of 1.2, 5.5 and 7.4 in vitro at 37°C. The effect of enzymes on the hydrolysis of prodrugs was also studied through incubation of these prodrugs at 37°C in human plasma and rat liver homogenates. The pharmacokinetic parameters of selected prodrugs and the liberated nap were studied after oral and intraperitoneal administration in male wistar rats. The results showed the hydrolysis of naproxen amides of amino acid esters to nap through two steps first by degradation of the ester moiety to form the amide of nap with amino acid and the second was through the degradation of the amide link to liberate nap. The two reactions were followed and studied kinetically where K1 and K2 (rate constants of degradation) is reported. The hydrolysis of prodrugs was faster in liver homogenates than in plasma. The relative bioavailability of the liberated nap in vivo was higher in case of prodrug containing ethyl glycinate moiety than that occupied L-valine ethyl ester moiety. Each of nap. prodrugs containing ethyl glycinate and L-valine ethyl ester moieties appears promising in liberating nap, decreasing direct GI side effect and consequently their colorectal cancer chemopreventive activity.
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      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.006
       
  • Development of pyrrolo[2,1-c][1,4]benzodiazepine β-glucosideprodrugs for
           selective therapy of cancer
    • Authors: Praveen Reddy Adiyala; Venkatesh Tekumalla; Ibrahim Bin Sayeed; V. Lakshma Nayak; Apoorva Nagarajan; Mohd Adil Shareef; Burri Nagaraju; Ahmed Kamal
      Abstract: Publication date: Available online 2 December 2017
      Source:Bioorganic Chemistry
      Author(s): Praveen Reddy Adiyala, Venkatesh Tekumalla, Ibrahim Bin Sayeed, V. Lakshma Nayak, Apoorva Nagarajan, Mohd Adil Shareef, Burri Nagaraju, Ahmed Kamal
      Cancer chemotherapy has several limitations such as often insufficient differentiation between malign tissue and benign tissue. The clinical utility of the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are inadequate because of the lack of selectivity for tumor tissues, high reactivity of the pharmacophoric imine functionality, low water solubility, and stability. To address these limitations two new β-glucoside prodrugs of PBDs have been synthesized and evaluated for their potential use in selective therapy of solid tumors by ADEPT. The preliminary studies reveal the prodrugs are much less toxic compared to the parent moieties. These prodrugs are activated by β-glucosidase to produce the active cytotoxic moiety signifying their utility in ADEPT of cancer. The prodrugs 1a and 1b were evaluated for their cytotoxic activity in three human cancer cell lines, i.e, A375, MCF-7 and HT-29 by employing MTT assay. The results reveal that the prodrugs have shown significant cytotoxic activity in the presence of enzyme. Another important property of these molecules is their enhanced water solubility and stability, which are essential for a molecule to be an effective drug.
      Graphical abstract image

      PubDate: 2017-12-13T02:57:15Z
      DOI: 10.1016/j.bioorg.2017.12.002
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2017-11-16T03:53:07Z
      DOI: 10.1016/j.bioorg.2017.10.005
       
 
 
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