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  Subjects -> CHEMISTRY (Total: 841 journals)
    - ANALYTICAL CHEMISTRY (50 journals)
    - CHEMISTRY (593 journals)
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CHEMISTRY (593 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 8)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26)
ACS Catalysis     Full-text available via subscription   (Followers: 34)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 23)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 233)
ACS Photonics     Full-text available via subscription   (Followers: 11)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 7)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 50)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 55)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 14)
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 Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 19)
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: 19)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 68)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 26)
American Journal of Plant Physiology     Open Access   (Followers: 14)
American Mineralogist     Hybrid Journal   (Followers: 14)
Analyst     Full-text available via subscription   (Followers: 40)
Angewandte Chemie     Hybrid Journal   (Followers: 222)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 213)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 3)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 15)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 295)
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: 4)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 121)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 98)
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: 3)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 66)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 6)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 8)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 4)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 13)
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: 23)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 19)
Chemical Reviews     Full-text available via subscription   (Followers: 176)
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: 57)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 26)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 142)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 18)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 258)
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: 3)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 9)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Clay Minerals     Full-text available via subscription   (Followers: 10)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 7)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 18)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 2)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 2)
Copernican Letters     Open Access   (Followers: 1)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 3)
CrystEngComm     Full-text available via subscription   (Followers: 12)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 58)
Dalton Transactions     Full-text available via subscription   (Followers: 22)
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: 4)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Elements     Full-text available via subscription   (Followers: 2)
Environmental Chemistry     Hybrid Journal   (Followers: 8)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)
Environmental Science : Nano     Partially Free   (Followers: 1)
Environmental Toxicology & Chemistry     Hybrid Journal   (Followers: 17)

        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  [3044 journals]
  • N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-β-alanines and their
           derivatives as inhibitors of human carbonic anhydrases
    • Authors: Irena Vaškevičienė; Vaida Paketurytė; Asta Zubrienė; Kristina Kantminienė; Vytautas Mickevičius; Daumantas Matulis
      Pages: 16 - 29
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Irena Vaškevičienė, Vaida Paketurytė, Asta Zubrienė, Kristina Kantminienė, Vytautas Mickevičius, Daumantas Matulis
      A series of N-substituted and N,N-disubstituted β-amino acids and their derivatives bearing benzenesulfonamide moiety were designed and synthesized in search of compounds that would be high-affinity and selective inhibitors of human carbonic anhydrases (CA). There are 12 catalytically active human CA isoforms, the cytosolic CA I, CA II, CA III, CA VII, and CA XIII, secreted CA VI, the mitochondrial CA VA and CA VB, membrane-associated CA IV, and transmembrane CA IX, CA XII, and CA XIV. The di-bromo meta-substituted compounds exhibited low nanomolar dissociation constants and over 10-fold selectivity for mitochondrial isozyme CA VB, implicated in diseases of the central nervous system and obesity. These compounds can be used for further development as inhibitors of significant binding affinity and selectivity towards CA VB isozyme.
      Graphical abstract image

      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.08.017
      Issue No: Vol. 75 (2017)
       
  • Synthesis of thiobarbituric acid derivatives: In vitro α-glucosidase
           inhibition and molecular docking studies
    • Authors: Assem Barakat; M. Ali; Abdullah Mohammed Al-Majid; Sammer Yousuf; M. Iqbal Choudhary; Ruqaiya Khalil; Zaheer Ul-Haq
      Pages: 99 - 105
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Assem Barakat, M. Ali, Abdullah Mohammed Al-Majid, Sammer Yousuf, M. Iqbal Choudhary, Ruqaiya Khalil, Zaheer Ul-Haq
      Synthesis, structure, and evaluation of in vitro α-glucosidase enzyme inhibition of a new class of diethylammonium salts of aryl substituted thiobarbituric acid is described. This protocol is straight, environmentally benign and efficient, involving Aldol-Michael addition reaction in one pot fashion. The 3D chemical structures of the synthesized compounds were assigned based on spectroscopic methods and X-ray single crystal diffraction analyses. All synthesized compounds 3a-3n were evaluated for their in vitro α-glucosidase enzyme inhibitory activity, whereas acarbose was used as the standard drug (IC50 =840±1.73µM). All tested compounds were found to possess varying degree of α-glucosidase enzyme inhibition activity with (IC50 =19.46±1.84–415.8±4.0µM). Compound 3i (IC50 =19.4±1.84µM) exhibited the highest activity. To the best of knowledge this is the first report of the in vitro α-glucosidase enzyme inhibition by the diethylamonium salts of aryl substituted thiobarbituric acid. Furthermore, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites.
      Graphical abstract image

      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.003
      Issue No: Vol. 75 (2017)
       
  • Molecular docking and QSAR analyses of aromatic heterocycle
           thiosemicarbazone analogues for finding novel tyrosinase inhibitors
    • Authors: Huanhuan Dong; Jing Liu; Xiaoru Liu; Yanying Yu; Shuwen Cao
      Pages: 106 - 117
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Huanhuan Dong, Jing Liu, Xiaoru Liu, Yanying Yu, Shuwen Cao
      A collection of 36 thiosemicarbazone analogues possessed a broad span of tyrosinase inhibitory activities was designed and obtained. Robust and reliable CoMFA and CoMSIA models were gained to predict the structure–activity relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend upon molecular shape, size, and charge. The sterically bulky group at the C-4 position of the thiophene ring contributed a high capacity for biological activity. Some bulky substituents at the C1-position and C12-position, and electron-negative groups at the C3-position, helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and detailed information about binding mode, affinity, and the principal mechanism between the ligands and tyrosinase. Based on these, a prospective structure modification and optimization of the most potent compound, T32, was suggested for further research.
      Graphical abstract image

      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.07.002
      Issue No: Vol. 75 (2017)
       
  • Novel Diphenylthiazole Derivatives with Multi-Target Mechanism: Synthesis,
           Docking study, Anticancer and Anti-Inflammatory Activities
    • Authors: Ahmed H. Abdelazeem; Mohammed T. El-Saadi; Eman G. Said; Bahaa G.M. Youssif; Hany A. Omar; Samir M. El-Moghazy
      Pages: 127 - 138
      Abstract: Publication date: Available online 12 September 2017
      Source:Bioorganic Chemistry
      Author(s): Ahmed H. Abdelazeem, Mohammed T. El-Saadi, Eman G. Said, Bahaa G.M. Youssif, Hany A. Omar, Samir M. El-Moghazy
      Over the last few decades, a growing body of studies addressed the anticancer activity of NSAIDs, particularly selective COX-2 inhibitors. However, their exact molecular mechanism still unclear and not fully investigated. In this regard, a novel series of compounds bearing a COXs privilege scaffold, diphenyl thiazole, was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines. The most active compounds 10b, 14a,b, 16a, 17a,b and 18b were evaluated in vitro for COX-1/COX-2 inhibitory activity. These compounds were suggested to exert their anticancer activity through a multi-target mechanism based on their structural features. Thus, compounds 10b and 17b with the least IC50 values in MTT assay were tested against three known anticancer targets; EGFR, BRAF and tubulin. Compounds 10b and 17b showed remarkable activity against EGFR with IC50 values of 0.4 and 0.2 μM, respectively and good activity against BRAF with IC50 values of 1.3 and 1.7 μM, respectively. In contrast, they showed weak activity in tubulin polymerization assay. The in vivo anti-inflammatory potential was assessed and interestingly, compound 17b was the most potent compound. Together, this study offers some important insights into the correlation between COXs inhibition and cancer treatment. Additionally, the results demonstrated the promising activity of these compounds with a multi-target mechanism as good candidates for further development into potential anticancer agents.
      Graphical abstract image

      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.009
      Issue No: Vol. 75 (2017)
       
  • Biology-oriented drug synthesis (BIODS) of
           2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives, in
           vitro α-amylase inhibitory activity and in silico studies
    • Authors: Muhammad Taha; Syahrul Imran; Nor Hadiani Ismail; Manikandan Selvaraj; Fazal Rahim; Sridevi Chigurupati; Hayat Ullah; Fahad Khan; Uzma Salar; Muhammad Tariq Javid; Shantini Vijayabalan; Khalid Zaman; Khalid Mohammed Khan
      Pages: 1 - 9
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Muhammad Taha, Syahrul Imran, Nor Hadiani Ismail, Manikandan Selvaraj, Fazal Rahim, Sridevi Chigurupati, Hayat Ullah, Fahad Khan, Uzma Salar, Muhammad Tariq Javid, Shantini Vijayabalan, Khalid Zaman, Khalid Mohammed Khan
      A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1 −23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50 =0.38±0.82µM) and 23 (IC50 =1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50 =1.77–2.98µM when compared with the standard acarbose (IC50 =1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.001
      Issue No: Vol. 74 (2017)
       
  • New heterocyclic compounds from Ranunculus ternatus Thunb.
    • Authors: Zi-ming Feng; Zhi-lai Zhan; Ya-nan Yang; Jian-shuang Jiang; Pei-cheng Zhang
      Pages: 10 - 14
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Zi-ming Feng, Zhi-lai Zhan, Ya-nan Yang, Jian-shuang Jiang, Pei-cheng Zhang
      Five new heterocyclic compounds, 5-α-d-fructofuranosylmethyl-furfural (1), 5-β-d-fructofuranosylmethyl-furfural (2), 5-β-d-fructopyranosylmethyl-furfural (3), 4-(2-((2S-2,3-dihydroxypropoxy)methyl)-5-formyl-1H-pyrrol-1-yl)butanoic acid (4), and 3S,4S-4,5,8-trihydroxy-3-(prop-1-en-2-yl)isochroman-1-one (5), were obtained from the root of Ranunculus ternatus Thunb., which is a traditional Chinese anti-tuberculosis medicine. Their structures were elucidated by UV, IR, HRESIMS, NMR data, and the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Notably, compounds 1–3 are rarely occurring furfural fructosides in natural sources. These heterocyclic compounds could be further studied for the synthetic chemists and pharmacologists due to the source and structural properties.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.004
      Issue No: Vol. 74 (2017)
       
  • Catalytic amidolysis of amino acid p-nitroanilides using transition state
           analogue imprinted artificial enzymes: Cooperative effect of pyridine
           moiety
    • Authors: Mathew Divya; Thomas Benny; Philip Christy; E.P. Aparna; K.S. Devaky
      Pages: 91 - 103
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Mathew Divya, Thomas Benny, Philip Christy, E.P. Aparna, K.S. Devaky
      Enzyme-like polymer catalysts with the imprints of phosphonate transition state analogue (TSA) lined along with imidazole and pyridine moieties were synthesized using methacryloyl-l-histidine and 4-vinylpyridine as the functional monomers and phenyl-1-(N-benzyloxycarbonylamino)-2-(phenyl)ethyl phosphonate – the TSA of hydrolytic reaction as the template for the amidolysis of N-benzyloxycarbonyl-l-phenylalanine p-nitroanilide (Z-l-Phe-PNA). Polymers containing different functional groups can act together to provide catalytic activity and selectivity superior to what can be obtained from monofunctional analogues. The higher rate acceleration exhibited by the bifunctional polymer over the monofunctional polymers indicates cooperative catalysis of imidazole and pyridine moieties. The optimum catalytic competence is shown by the bifunctional polymer containing imidazole and pyridine moieties in 2:1M ratio which may be due to alignment of the functional groups in proper H-bond distance. In addition to the non-covalent interactions like hydrogen bonding or π-stacking interactions between the functional groups of the polymer and the template, 3D-microcavities complementary to the geometry of the template are necessary for effective shape selective binding. Michaelis-Menten kinetics implies that only the catalysts with imidazole moieties act as enzyme-like catalysts and imidazole is the key catalytic function of the enzyme mimics.
      Graphical abstract image

      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.015
      Issue No: Vol. 74 (2017)
       
  • A new cerebroside from the twigs of Lindera glauca (Sieb. et Zucc.) Blume
    • Authors: Jae Sik Yu; Eunjung Moon; Ki Hyun Kim
      Pages: 122 - 125
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Jae Sik Yu, Eunjung Moon, Ki Hyun Kim
      Lindera glauca (Sieb. et Zucc.) Blume (Lauraceae) has been used to treat rheumatic arthritis, stroke, and cardiac pain. Phytochemical investigation of twigs of L. glauca (Sieb. et Zucc.) Blume resulted in the isolation and identification of a new cerebroside, glaucerebroside (1). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, chemical reactions, and LC/MS analysis. Compound 1 is a relatively rare cerebroside with l-threo-configuration of the sphingosine part. This is the second example of identification of a cerebroside from the family Lauraceae. Compound 1 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 cells, with an IC50 value of 23.84μM without inducing cell toxicity. This study suggests that glaucerebroside (1) can be an excellent candidate for development of novel anti-neuroinflammatory agents.
      Graphical abstract image

      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.016
      Issue No: Vol. 74 (2017)
       
  • Synthesis and biological evaluation of quinazolinone-based hydrazones with
           potential use in Alzheimer’s disease
    • Authors: Zahra Haghighijoo; Omidreza Firuzi; Bahram Hemmateenejad; Saeed Emami; Najmeh Edraki; Ramin Miri
      Pages: 126 - 133
      Abstract: Publication date: Available online 25 July 2017
      Source:Bioorganic Chemistry
      Author(s): Zahra Haghighijoo, Omidreza Firuzi, Bahram Hemmateenejad, Saeed Emami, Najmeh Edraki, Ramin Miri
      Discovering multifunctional agents for the treatment of Alzheimer’s disease (AD) is an attractive therapeutic approach. BACE1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors may play a pivotal role in treating AD. Therefore, the discovery of novel non-peptide BACE1 inhibitors with desirable blood brain barrier permeability is a favorable approach for treatment. Moreover, the antioxidant potential of a drug could serve as an added value for designing dual-acting therapeutic agents. Here, we report the design, synthesis and biological evaluation of quinazolinone-hydrazone derivatives as new multi-target candidates for the treatment of AD. The compounds were investigated for their in vitro BACE1 inhibitory potential using a FRET-based enzymatic assay and also screened for antioxidant activity using DPPH. Among them, compound 4h bearing a 2,3-dichlorophenyl moiety showed the highest activity with an IC50 value of 3.7 μM against BACE1. In addition, compound 4i with a 2,4-dihydroxyphenyl scaffold demonstrated moderate BACE1 inhibitory activity (IC50 = 27.6 μM) with a significant antioxidant effect (IC50 = 8.4 μM). Furthermore, docking studies revealed strong interaction between compound 4h and the key residues of BACE1 active site. These results demonstrate that quinazolinone-hydrazone derivatives represent a valuable scaffold for the discovery of novel non-peptidic BACE1 inhibitors.
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      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.014
      Issue No: Vol. 74 (2017)
       
  • Synthesis and study of the α-amylase inhibitory potential of
           thiadiazole quinoline derivatives
    • Authors: Muhammad Taha; Muhammad Tariq Javid; Syahrul Imran; Manikandan Selvaraj; Sridevi Chigurupati; Hayat Ullah; Fazal Rahim; Fahad Khan; Jahidul Islam Mohammad; Khalid Mohammed Khan
      Pages: 179 - 186
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Muhammad Taha, Muhammad Tariq Javid, Syahrul Imran, Manikandan Selvaraj, Sridevi Chigurupati, Hayat Ullah, Fazal Rahim, Fahad Khan, Jahidul Islam Mohammad, Khalid Mohammed Khan
      α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1−30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.003
      Issue No: Vol. 74 (2017)
       
  • Synthesis, molecular docking studies of coumarinyl-pyrazolinyl substituted
           thiazoles as non-competitive inhibitors of mushroom tyrosinase
    • Authors: Aamer Saeed; Parvez Ali Mahesar; Pervaiz Ali Channar; Qamar Abbas; Fayaz Ali Larik; Mubashir Hassan; Hussain Raza; Sung-Yum Seo
      Pages: 187 - 196
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Aamer Saeed, Parvez Ali Mahesar, Pervaiz Ali Channar, Qamar Abbas, Fayaz Ali Larik, Mubashir Hassan, Hussain Raza, Sung-Yum Seo
      A series of coumarinyl-pyrazolinyl substituted thiazoles derivatives were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that all of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. In particular, 3-(5-(4-(benzyloxy)-3-methoxyphenyl)-1-(4-(4-bromophenyl)thiazol-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one (7j) exhibited the most potent tyrosinase inhibitory activity with IC50 value 0.00458±0.00022μM compared with the IC50 value of kojic acid is 16.84±0.052μM. The inhibition mechanism analyzed by Lineweaver–Burk plots revealed that the type of inhibition of compound 7j on tyrosinase was noncompetitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compound 7a showed the highest binding affinity (−10.20kcal/mol) with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compound 7j may serve asa structural template for the design and development of novel tyrosinase inhibitors.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.002
      Issue No: Vol. 74 (2017)
       
  • Tannic acid affects the phenotype of Staphylococcus aureus resistant to
           tetracycline and erythromycin by inhibition of efflux pumps
    • Authors: Saulo R. Tintino; Cícera D. Morais-Tintino; Fábia F. Campina; Maria do S. Costa; Irwin R.A. Menezes; Yedda Maria L.S. de Matos; João T. Calixto-Júnior; Pedro S. Pereira; José P. Siqueira-Junior; Teresa C. Leal-Balbino; Henrique D.M. Coutinho; Valdir Q. Balbino
      Pages: 197 - 200
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Saulo R. Tintino, Cícera D. Morais-Tintino, Fábia F. Campina, Maria do S. Costa, Irwin R.A. Menezes, Yedda Maria L.S. de Matos, João T. Calixto-Júnior, Pedro S. Pereira, José P. Siqueira-Junior, Teresa C. Leal-Balbino, Henrique D.M. Coutinho, Valdir Q. Balbino
      The widespread use of antibiotics created selective pressure for the emergence of strains that would persist despite antibiotic toxicity. The bacterial resistance mechanisms are several, with efflux pumps being one of the main ones. These pumps are membrane proteins with the function of removing antibiotics from the cell cytoplasm. Due to this importance, the aim of this work was to evaluate the inhibitory effect of tannic acid against efflux pumps expressed by the Staphylococcus aureus RN4220 and IS-58 strains. The efflux pump inhibition was assayed using a sub-inhibitory concentration of efflux pump standard inhibitors and tannic acid (MIC/8), observing their capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. The MICs of EtBr and antibiotics were significantly different in the presence of tannic acid, indicating the inhibitory effect of this product against efflux pumps of both strains. These results indicate the possible usage of tannic acid asan inhibitor and an adjuvant in the antibiotic therapy against multidrug resistant bacteria (MDR).
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.004
      Issue No: Vol. 74 (2017)
       
  • Structure-activity relationships and molecular docking of thirteen
           synthesized flavonoids as horseradish peroxidase inhibitors
    • Authors: Reguia Mahfoudi; Amar Djeridane; Khedidja Benarous; Emile M. Gaydou; Mohamed Yousfi
      Pages: 201 - 211
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Reguia Mahfoudi, Amar Djeridane, Khedidja Benarous, Emile M. Gaydou, Mohamed Yousfi
      For the first time, the structure–activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as peroxidase co-substrate. The results show that these flavonoids exhibit a great capacity to inhibit peroxidase with Ki values ranged from 0.14±0.01 to 65±0.04mM. Molecular docking has been achieved using Auto Dock Vina program to discuss the nature of interactions and the mechanism of inhibition. According to the docking results, all the flavonoids have shown great binding affinity to peroxidase. These molecular modeling studies suggested that pyran-4-one cycle acts as an inhibition key for peroxidase. Therefore, potent peroxidase inhibitors are flavonoids with these structural requirements: the presence of the hydroxyl (OH) group in 7, 5 and 4′ positions and the absence of the methoxy (O–CH3) group. Apigenin contributed better in HRP inhibitory activity. The present study has shown that the studied flavonoids could be promising HRP inhibitors, which can help in developing new molecules to control thyroid diseases.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.001
      Issue No: Vol. 74 (2017)
       
  • Pyrazole-hydrazone derivatives as anti-inflammatory agents: Design,
           synthesis, biological evaluation, COX-1,2/5-LOX inhibition and docking
           study
    • Authors: Mohamed A. Abdelgawad; Madlen B. Labib; Mahmoud Abdel-Latif
      Pages: 212 - 220
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Mohamed A. Abdelgawad, Madlen B. Labib, Mahmoud Abdel-Latif
      A new series of pyrazole-hydrazone derivatives 4a-i were designed and synthesized, their chemical structures were confirmed by IR, 1H NMR, 13C NMR, MS spectral data and elemental analysis. IC50 values for all prepared compounds to inhibit COX-1, COX-2 and 5-LOX enzymes were determined in vitro. Compounds 4a (IC50 =0.67μM) and 4b (IC50 =0.58μM) showed better COX-2 inhibitory activity than celecoxib (IC50 =0.87μM) with selectivity index (SI=8.41, 10.55 in sequent) relative to celecoxib (SI=8.85). Also, compound 4a and 4b exhibited superior inhibitory activity against 5-LOX (IC50 =1.92, 2.31μM) higher than zileuton (IC50 =2.43μM). All target pyrazoles were screened for their ability to reduce nitric oxide production in LPS stimulated peritoneal macrophages. Compounds 4a, 4b, 4f and 4i displayed concentration dependent reduction and were screened for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema assay. Compound 4f showed the highest anti-inflammatory activity (% edema inhibition=15–20%) at all doses when compared to reference drug celecoxib (% edema inhibition=15.7–17.5%). Docking studies were carried out to investigate the interaction of target compounds with COX-2 enzyme active site.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.014
      Issue No: Vol. 74 (2017)
       
  • A new lignan and a new alkaloid, and α-glucosidase inhibitory compounds
           from the grains of Echinochloa utilis Ohwi & Yabuno
    • Authors: Thi Trang Nguyen; Duc Hung Nguyen; Bing Tian Zhao; Duc Dat Le; Du Hyung Choi; Young Ho Kim; Thi Hoai Nguyen; Mi Hee Woo
      Pages: 221 - 227
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Thi Trang Nguyen, Duc Hung Nguyen, Bing Tian Zhao, Duc Dat Le, Du Hyung Choi, Young Ho Kim, Thi Hoai Nguyen, Mi Hee Woo
      A new lignan, utilisin (1), and a new alkaloid, echinoutilin (2), together with eleven known compounds 3–13 were isolated from the grains of Echinochloa utilis Ohwi & Yabuno. Their structures were identified through the analysis of spectroscopic data. The absolute configuration of 2 was determined by Mosher’s method. These compounds were evaluated for α-glucosidase inhibitory activity. Among them, compounds 2, 3 and 6 exhibited considerable α-glucosidase inhibitory activity with IC50 values of 42.1±1.3, 58.9±3.7, and 40.9±1.1μM, respectively. The results indicate that the grains of E. utilis will be useful in the treatment of diabetes control agents.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.007
      Issue No: Vol. 74 (2017)
       
  • Thiazolo[4,5-d]pyridazine analogues as a new class of dihydrofolate
           reductase (DHFR) inhibitors: Synthesis, biological evaluation and
           molecular modeling study
    • Authors: Menna A. Ewida; Dalal A. Abou El Ella; Deena S. Lasheen; Heba A. Ewida; Yomna I. El-Gazzar; Hussein I. El-Subbagh
      Pages: 228 - 237
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Menna A. Ewida, Dalal A. Abou El Ella, Deena S. Lasheen, Heba A. Ewida, Yomna I. El-Gazzar, Hussein I. El-Subbagh
      A new series of 1,3-thiazoles and thiazolo[4,5-d]pyridazine both bearing the 2-thioureido function were designed, synthesized and evaluated for their invitro DHFR inhibition and antitumor activities. Compound 26 proved to be the most active DHFR inhibitor (IC50 of 0.06μM). Compound 4, 20 and 21 showed in vitro antitumor activity against a collection of cancer cell lines. Compound 26 proved lethal to HS 578T breast cancer cell line with IC50 value of 0.8μM, inducing cell cycle arrest and apoptosis. Molecular modeling studies concluded that recognition with key amino acids Phe 31 and Arg 22 is essential for DHFR binding. The obtained model could be useful for the development of new class of DHFR inhibitors.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.010
      Issue No: Vol. 74 (2017)
       
  • The synthesis of novel sulfamides derived from β-benzylphenethylamines as
           acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes
           inhibitors
    • Authors: Akın Akıncıoğlu; Ebutalib Kocaman; Hülya Akıncıoğlu; Ramin Ekhteiari Salmas; Serdar Durdagi; İlhami Gülçin; Claudiu T. Supuran; Süleyman Göksu
      Pages: 238 - 250
      Abstract: Publication date: October 2017
      Source:Bioorganic Chemistry, Volume 74
      Author(s): Akın Akıncıoğlu, Ebutalib Kocaman, Hülya Akıncıoğlu, Ramin Ekhteiari Salmas, Serdar Durdagi, İlhami Gülçin, Claudiu T. Supuran, Süleyman Göksu
      In this study, a series of novel β-benzylphenethylamines and their sulfamide derivatives were synthesized starting from (Z)-2,3-diphenylacrylonitriles. Pd-C catalysed hydrogenation of diphenylacrylonitriles, reduction of propanenitriles with LiAlH4 in the presence of AlCl3 followed by addition of conc. HCl afforded β-benzylphenethylamine hydrochloride salts. The reactions of these amine hydrochloride salts with chlorosulfonyl isocyanate (CSI) in the presence of tert-BuOH and excess Et3N gave sulfamoylcarbamates. Removing of Boc group from the synthesized sulfamoylcarbamates with trifluoroacetic acid (TFA) yielded novel sulfamides in good yields. These novel sulfamides derived from β-benzylphenethylamines were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with Ki values in the range of 0.278–2.260nM for hCA I, 0.187–1.478nM for hCA II, 0.127–2.452nM for AChE and 0.494–1.790nM for BChE. The inhibitory effects of the synthesized novel sulfamides derived from β-benzylphenethylamines were compared to those of acetazolamide and dorzolamide as clinical hCA I and II isoenzymes inhibitors and tacrine as a clinical AChE and BChE enzymes inhibitors. In addition to in vitro tests, molecular modeling approaches are implemented not only for prediction of the binding affinities of the compounds but also to study their inhibition mechanisms in atomic level at the catalytic domains.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.012
      Issue No: Vol. 74 (2017)
       
  • Enantioselectivity of Haloalkane Dehalogenase LinB on the Degradation of
           1,2-Dichloropropane: A QM/MM Study
    • Authors: Xiaowen Tang; Ruiming Zhang; Yanwei Li; Qingzhu Zhang; Wenxing Wang
      Pages: 16 - 23
      Abstract: Publication date: Available online 12 May 2017
      Source:Bioorganic Chemistry
      Author(s): Xiaowen Tang, Ruiming Zhang, Yanwei Li, Qingzhu Zhang, Wenxing Wang
      The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8 kcal/mol for the (R)-isomer and 24.0 kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.
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      PubDate: 2017-05-16T11:27:51Z
      DOI: 10.1016/j.bioorg.2017.04.015
      Issue No: Vol. 73 (2017)
       
  • The anthraquinone emodin inhibits the non-exported FIKK kinase from
           Plasmodium falciparum
    • Authors: Benjamin C. Lin; Darcy R. Harris; Lucy M.D. Kirkman; Astrid M. Perez; Yiwen Qian; Janse T. Schermerhorn; Min Y. Hong; Dennis S. Winston; Lingyin Xu; Alexander M. Lieber; Matthew Hamilton; Gabriel S. Brandt
      Abstract: Publication date: Available online 18 September 2017
      Source:Bioorganic Chemistry
      Author(s): Benjamin C. Lin, Darcy R. Harris, Lucy M.D. Kirkman, Astrid M. Perez, Yiwen Qian, Janse T. Schermerhorn, Min Y. Hong, Dennis S. Winston, Lingyin Xu, Alexander M. Lieber, Matthew Hamilton, Gabriel S. Brandt
      The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50 = 2 μM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function.
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      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.011
       
  • Chemical synthesis and in silico molecular modeling of novel pyrrolyl
           benzohydrazide derivatives: their biological evaluation against enoyl ACP
           reductase (InhA) and Mycobacterium tuberculosis
    • Authors: Shrinivas D. Joshi; Uttam A. More; Sheshagiri R. Dixit; Sunil V. Balmi; Basavaraj G. Kulkarni; Geeta Ullagaddi; Christian Lherbet; Tejraj M. Aminabhavi
      Abstract: Publication date: Available online 12 September 2017
      Source:Bioorganic Chemistry
      Author(s): Shrinivas D. Joshi, Uttam A. More, Sheshagiri R. Dixit, Sunil V. Balmi, Basavaraj G. Kulkarni, Geeta Ullagaddi, Christian Lherbet, Tejraj M. Aminabhavi
      In efforts to develop new antitubercular agents, we report here the synthesis of a series of novel pyrrole hydrazine derivatives. The molecules were evaluated against inhibitors of InhA, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of the mycobacterial cell wall as well as inhibitors of Mycobacterium tuberculosis H37Rv. The binding mode of compounds at the active site of enoyl-ACP reductase was explored using the surflex-docking method. The model suggests one or two H-bonding interactions between the compounds and the InhA enzyme. Some compounds exhibited good activities against InhA in addition to promising activities against M. tuberculosis.
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      PubDate: 2017-09-19T19:08:38Z
      DOI: 10.1016/j.bioorg.2017.09.008
       
  • The inhibitory activity of HL-7 and HL-10 peptide from scorpion venom
           (Hemiscorpius lepturus) on angiotensin converting enzyme: Kinetic and
           docking study
    • Authors: Zahra Setayesh-Mehr; Ahmad Asoodeh
      Abstract: Publication date: December 2017
      Source:Bioorganic Chemistry, Volume 75
      Author(s): Zahra Setayesh-Mehr, Ahmad Asoodeh
      The hypertension is one of the highest risk factors for stroke, myocardial infarction, vascular disease and chronic kidney disease. Angiotensin converting enzyme (ACE) has an important role in the physiological regulation of cardiovascular system. ACE inhibition is a key purpose for hypertension treatment. In this study, two peptides named HL-7 with the sequence of YLYELAR (MW: 927.07Da) and HL-10 with the sequence of AFPYYGHHLG (MW: 1161.28Da) were identified from scorpion venom of H. lepturus. The inhibitory activity of HL-7 and HL-10 was examined on rabbit ACE. The inhibition mechanisms were assayed by kinetic and docking studies. The IC50 values for ACE inhibition of HL-7 and HL-10 were 9.37µM and 17.22µM, respectively. Lineweaver-Burk plots showed that two peptides inhibited rabbit ACE with competitive manner. The molecular docking conformed experimental results and showed that the two peptides interacted with N-domain and C-domain active sites. Also, docking study revealed that the two peptides can form hydrogen and hydrophobic bonds at their binding sites. Both peptides had higher affinity to N-domain. Our results showed that HL-7 exhibited more strong interactions with amino acids at active site. It seems that HL-10 peptide could occupy more space, thereby inhibiting the substrate entrance to active site.
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      PubDate: 2017-09-13T12:08:47Z
       
  • Syntheses of 4,6-dihydroxy pyrimidine diones, their urease inhibition, in
           vitro, in silico, and kinetic studies
    • Authors: Munira Taj Muhammad; Khalid Mohammed Khan; Arshia; Ajmal Khan; Fiza Arshad; Bibi Fatima; M. Iqbal Choudhary; Naima Syed; Syed Tarique Moin
      Abstract: Publication date: Available online 11 September 2017
      Source:Bioorganic Chemistry
      Author(s): Munira Taj Muhammad, Khalid Mohammed Khan, Arshia, Ajmal Khan, Fiza Arshad, Bibi Fatima, M. Iqbal Choudhary, Naima Syed, Syed Tarique Moin
      A library of 4,6-dihydroxy pyrimidine diones 1-35 were synthesized and evaluated for their urease inhibitory activity. Structure-activity relationships and mechanism of inhibition were also studied. All compounds were found to be active with IC50 values 22.6 ± 1.14-117.4 ± 0.73 µM in comparison to standard (IC50 = 21.2 ± 1.3 µM). Kinetics studies on the most active compounds 2-7, 16, 17, 28, and 33 were performed to investigate their mode of inhibition and dissociation constants Ki . Compounds 2, 3, 7, 16, 28, and 33 were found to be mixed-type of inhibitors with Ki values in the range of 7.91 ± 0.024-13.03 ± 0.013 µM, whereas, compounds 4-6, and 17 were found to be non-competitive inhibitors with Ki values in the range of 9.28 ± 0.019- 13.05 ± 0.023 µM. In silico study was also performed, a good correlation was observed between experimental and docking studies. This study is continuation of our previously reported urease inhibitory activity of pyrimidine diones, representing potential leads for further studies as treatment caused by ureolytic bacteria.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.08.018
       
  • Synthesis and in vitro Study of Benzofuran Hydrazone Derivatives as Novel
           Alpha-Amylase Inhibitor
    • Authors: Muhammad Taha; Syed Adnan Ali Shah; Syahrul Imran; Muhammad Afifi; Sridevi Chigurpati; Manikandan Selvaraj; Fazal Rahim; Hayat Ullah; Khalid Zaman; Shantini Vijayabalan
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Syed Adnan Ali Shah, Syahrul Imran, Muhammad Afifi, Sridevi Chigurpati, Manikandan Selvaraj, Fazal Rahim, Hayat Ullah, Khalid Zaman, Shantini Vijayabalan
      The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC50 value ranging between 1.078±0.19 to 2.926±0.05 µM when compared with acarbose having IC50= 0.62±0.22 µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.002
       
  • Nitric oxide inhibitory daphnane diterpenoids as potential
           anti-neuroinflammatory agents for AD from the twigs of Trigonostemon
           thyrsoideus
    • Authors: Feng Liu; Xueyuan Yang; Jun Ma; Yuling Yang; Chunfeng Xie; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Yuanqiang Guo
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Feng Liu, Xueyuan Yang, Jun Ma, Yuling Yang, Chunfeng Xie, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo
      The extensive pathology studies revealed that Alzheimer’s disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1−4) and eight known (5−12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1−4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.007
       
  • New indole-based chalconoids as tubulin-targeting antiproliferative agents
    • Authors: Hassan Mirzaei; Mohammad Shokrzadeh; Mona Modanloo; Ali Ziar; Gholam Hossein Riazi; Saeed Emami
      Abstract: Publication date: Available online 7 September 2017
      Source:Bioorganic Chemistry
      Author(s): Hassan Mirzaei, Mohammad Shokrzadeh, Mona Modanloo, Ali Ziar, Gholam Hossein Riazi, Saeed Emami
      Tubulin-targeting compounds have a broad anticancer spectrum and are an important class of chemotherapeutic agents. Due to the importance of 3-bromo-3,5-dimethoxyphenyl scaffold in the anticancer activity of microtubule inhibitors such as crolibulin (EPC2407), we introduced this functionality into the indole-derived chalcones. Thus, we describe here the synthesis and biological evaluation of new indole-based chalconoids as tubulin-targeting antiproliferative agents. The best result was obtained by compound 9b against A549 cell with IC50 of 4.3 µg/mL, being more potent than the reference drug etoposide. Further biological evaluations revealed that compound 9b can inhibit tubulin polymerization and decrease the mitochondrial thiol content, resulting the induction of apoptosis in cancer cells. Docking studies with tubulin indicated that compound 9b could bind to the colchicine binding site.
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      PubDate: 2017-09-13T12:08:47Z
      DOI: 10.1016/j.bioorg.2017.09.005
       
  • Traditional Chinese Medicinal Herbs as potential AChE inhibitors for
           anti-Alzheimer’s Disease: A review
    • Authors: Yingying Jiang; Hongwei Gao; Gulmira Turdu
      Abstract: Publication date: Available online 6 September 2017
      Source:Bioorganic Chemistry
      Author(s): Yingying Jiang, Hongwei Gao, Gulmira Turdu
      Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting 25 million people worldwide, and cholinergic hypothesis is considered as an important hypotheses in the processes of improving cognitive function and recognition skills in recent years. For the long-term treatment of AD, traditional Chinese medicine are particularly suitable for drug discovery. In this review, we sum up six traditional Chinese medicinal herbs concerned with development of AChEIs, including Herba Epimedii, Coptis Chinensis Franch, Rhizoma Curcumae Longae, Green tea, Ganoderma, Panax Ginseng. The listed compounds based on these herbs are belonging to six classes Flavonoids, Alkaloids, Ketones, Polyphenols, Terpenoid and Saponins, respectively. These compounds could be very promising agents in the search for potent anti-Alzheimer’s drugs.
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      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.09.004
       
  • Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum:
           structures, PTP1B inhibitory activities, and interactions with PTP1B
    • Authors: Xiangrong Cao; Xueyuan Yang; Peixia Wang; Yue Liang; Feng Liu; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Yuanqiang Guo
      Abstract: Publication date: Available online 6 September 2017
      Source:Bioorganic Chemistry
      Author(s): Xiangrong Cao, Xueyuan Yang, Peixia Wang, Yue Liang, Feng Liu, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Yuanqiang Guo
      Protein tyrosine phosphatase 1B (PTP1B) has been regarded as a target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A−D (1−4) from the aerial parts of Hypericum longistylum. The structures of 1−4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1−4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.
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      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.09.001
       
  • Identification of new potent inhibitor of aldose reducatse from Ocimum
           basilicum
    • Authors: Huma Aslam Bhatti; Yildiz Tehseen; Kiran Maryam; Maliha Uroos; Bina S. Siddiqui; Abdul Hameed; Jamshed Iqbal
      Abstract: Publication date: Available online 5 September 2017
      Source:Bioorganic Chemistry
      Author(s): Huma Aslam Bhatti, Yildiz Tehseen, Kiran Maryam, Maliha Uroos, Bina S. Siddiqui, Abdul Hameed, Jamshed Iqbal
      Recent efforts is to develop cure for chronic diabetic complications results in the discovery of potent inhibitors against aldose reductase (AKR1B1, EC 1.1.1.21) whose role in diabetes is well-evident. In the present work, two new natural products were isolated from the ariel part of Ocimum basilicum;7-(3-hydroxypropyl)-3-methyl-8-β-O-D-glucoside-2H-chromen-2-one (1) and E-4-(6'-hydroxyhex-3'-en-1-yl)phenyl propionate (2) and confirmed their structures with different spectroscopic techniques including NMR spectroscopy etc. The isolated compounds (1, 2) were evaluated for in vitro inhibitory activity against aldose reductase (AKR1B1) and aldehyde reductase (AKR1A1). The natural product (1) showed better inhibitory activity for AKR1B1 with IC50 value of 2.095 ± 0.77 µM compare to standard sorbinil (IC50 = 3.14 ± 0.02 µM). Moreover, the compound (1) also showed multifolds higher activity (IC50 = 0.783 ± 0.07 µM) against AKR1A1 as compared to standard valproic acid (IC50 = 57.4 ± 0.89 µM). However, the natural product (2) showed slightly lower activity for AKR1B1 (IC50 = 4.324 ± 1.25 µM). Moreover, the molecular docking studies of the potent inhibitors were also performed to identify the putative binding modes within the active site of aldose/aldehyde reductases.
      Graphical abstract image

      PubDate: 2017-09-07T12:04:12Z
      DOI: 10.1016/j.bioorg.2017.08.011
       
  • Synthesis, characterization and DNA binding studies of platinum(II)
           complexes with benzimidazole derivative ligands
    • Authors: Özden Tarı; Fatma Gümüş; Leyla Açık; Betül Aydın
      Abstract: Publication date: Available online 1 September 2017
      Source:Bioorganic Chemistry
      Author(s): Özden Tarı, Fatma Gümüş, Leyla Açık, Betül Aydın
      The aim of this study was to synthesize and evaluate plasmid DNA interaction of new platinum(II) complexes with some 2-substituted benzimidazole derivatives as carrier ligands which may have potent anticancer activity and low toxicity. Twelve benzimidazole derivatives carrying indole, 2-/or 3-/or 4-methoxyphenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3,4,5-trimethoxystyryl, 3,4,5-trimethoxybenzylthio or dimethylamino ethyl groups in their position 2 and twelve platinum(II) complexes with these carrier ligands were synthesized. The chemical structure of the platinum complexes have been characterized by their elemental analysis and FIR, 1H NMR and mass spectra and their 1H NMR and FIR spectra were interpreted by comparison with those of the ligands. The interaction of all the ligands and their complexes with plasmid DNA and their restriction endonuclease reactions by BamHI and HindIII enzymes were studied by agarose gel electrophoresis. It was determined that complex 1 [dichloro-di(2-(1H-indole-3-yl)benzimidazole)platinum(II).2H2O] has stronger interaction than carboplatin and complex 10 [dichloro-di(2-(3,4,5-trimethoxystyryl)benzimidazole)platinum(II).2H2O] has stronger interaction than both carboplatin and cisplatin with plasmid DNA.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.015
       
  • Exploration of thioxothiazolidinone–sulfonate conjugates as a new class
           of aldehyde/aldose reductase inhibitors: A synthetic and computational
           investigation
    • Authors: Hina Andleeb; Yildiz Tehseen; Farrukh Jabeen; Imtiaz Khan; Jamshed Iqbal; Shahid Hameed
      Abstract: Publication date: Available online 31 August 2017
      Source:Bioorganic Chemistry
      Author(s): Hina Andleeb, Yildiz Tehseen, Farrukh Jabeen, Imtiaz Khan, Jamshed Iqbal, Shahid Hameed
      In the present study, the pharmacophore integration methodology provided an efficient access to a new library of thioxothiazolidinone–sulfonate conjugates (8a–r) from easily available synthetic precursors. The approach was excellently high yielding with flexible structural sites for chemical modifications. The designed hybrid scaffolds were assessed for aldehyde/aldose reductase inhibition activities. The results for the in vitro bioassays were promising with the identification of compound 8e as the lead and selective candidate for ALR2 inhibition with an IC50 value of 0.468 ± 0.003 µM as compared to 3.1 ± 0.2 µM for the standard (sorbinil), whereas compound 8o demonstrated high inhibitory potency for both ALR2 and ALR1 enzymes. Molecular modeling analysis of the potent compounds provided further insight into the biological properties where detailed binding mode analysis revealed that the conjugates (8a–r) were found stabilized in the active site of the enzymes through the development of a number of interactions with catalytic residues.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.009
       
  • SAR studies of some acetophenone phenylhydrazone based pyrazole
           derivatives as anticathepsin agents
    • Authors: Neera Raghav; Mamta Singh
      Abstract: Publication date: Available online 31 August 2017
      Source:Bioorganic Chemistry
      Author(s): Neera Raghav, Mamta Singh
      Cathepsins have emerged as promising molecular targets in a number of diseases such as Alzeimer’s, inflammation and cancer. Elevated cathepsin’s levels and decreased cellular inhibitor concentrations have emphasized the search for novel inhibitors of cathepsins. The present work is focused on the design and synthesis of some acetophenone phenylhydrazone based pyrazole derivatives as novel non peptidyl inhibitors of cathepsins B, H and L. The synthesized compounds after characterization have been explored for their inhibitory potency against cathepsins B, H and L. The results show that some of the synthesized compounds exhibit anti-catheptic activity with Ki value of the order of 10-10 M. Differential inhibitory effects have been observed for cathepsins B, H and L. Cathepsin L is inhibited more pronounced than cathepsin B and cathepsin H in that order.
      Graphical abstract image

      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.006
       
  • Is literature data useful for identifying enzyme catalysts for new
           substrates'-A case study on reduction of 1-aryl-2-alkanoates
    • Authors: Bård Helge Hoff; Eirik Sundby
      Abstract: Publication date: Available online 31 August 2017
      Source:Bioorganic Chemistry
      Author(s): Bård Helge Hoff, Eirik Sundby
      The use of literature data to identify catalysts for a novel transformation is a commonly used approach. Herein, we have evaluated if this is a viable strategy in enzyme catalysis, using asymmetric reduction of 1-aryl-2-alkanoates as a model system. The study, which includes data from 24 ketone substrates and 108 enzymes, clearly identifies pitfalls with this approach, but anyhow shows that literature data is highly useful for identification of enantioselective catalysts. By combining data for selectivity and rate useful catalyst for converting different substrates to their corresponding (R)- and (S)-enantiomers are highlighted.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.005
       
  • 5-Substituted 2-benzylidene-1-tetralone analogues as A1 and/or A2A
           antagonists for the potential treatment of neurological conditions
    • Authors: H.D. Janse van Rensburg; G. Terre'Blanche; M.M. van der Walt; L.J. Legoabe
      Abstract: Publication date: Available online 30 August 2017
      Source:Bioorganic Chemistry
      Author(s): H.D. Janse van Rensburg, G. Terre'Blanche, M.M. van der Walt, L.J. Legoabe
      Adenosine A1 and A2A receptors are attracting great interest as drug targets for their role in cognitive and motor deficits, respectively. Antagonism of both these adenosine receptors may offer therapeutic benefits in complex neurological diseases, such as Alzheimer’s and Parkinson’s disease. The aim of this study was to explore the affinity and selectivity of 2-benzylidene-1-tetralone derivatives as adenosine A1 and A2A receptor antagonists. Several 5-hydroxy substituted 2-benzylidene-1-tetralone analogues with substituents on ring B were synthesized and assessed as antagonists of the adenosine A1 and A2A receptors via radioligand binding assays. The results indicated that hydroxy substitution in the meta and para position of phenyl ring B, displayed the highest selectivity and affinity for the adenosine A1 receptor with Ki values in the low micromolar range. Replacement of ring B with a 2-amino-pyrimidine moiety led to compound 12 with an increase of affinity and selectivity for the adenosine A2A receptor. These substitution patterns led to enhanced adenosine A1 and A2A receptor binding affinity. The para-substituted 5-hydroxy analogue 3 behaved as an adenosine A1 receptor antagonists in a GTP shift assay performed with rat whole brain membranes expressing adenosine A1 receptors. In conclusion, compounds 3 and 12, showed the best adenosine A1 and A2A receptor affinity respectively, and therefore represent novel adenosine receptor antagonists that may have potential with further structural modifications as drug candidates for neurological disorders.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.013
       
  • Liquid phase combinatorial synthesis of 1,2,5-trisubstituted benzimidazole
           derivatives as human DHODH inhibitors
    • Authors: Nikum D. Sitwala; Vivek K. Vyas; Bhavesh C. Variya; Snehal S. Patel; Chirag C. Mehta; Dharmraj N. Rana; Manjunath D. Ghate
      Abstract: Publication date: Available online 30 August 2017
      Source:Bioorganic Chemistry
      Author(s): Nikum D. Sitwala, Vivek K. Vyas, Bhavesh C. Variya, Snehal S. Patel, Chirag C. Mehta, Dharmraj N. Rana, Manjunath D. Ghate
      The synthesis of 1,2,5-trisubstituted benzimidazole derivatives was carried out using liquid phase combinatorial approach using soluble polymer assisted support (PEG5000). Synthesized compounds were characterized by FTIR, ESI-MS, 1H NMR and 13C NMR. The purity of compounds were confirmed with HPLC analysis. Compounds were also docked into the binding site of human dihydroorotate dehydrogenase (hDHODH). The synthesized compounds were screened for hDHODH enzyme inhibition assay using brequinar as standard compound. The synthesized compounds demonstrated comparative biological activity. Synthesized compound 8d and 8e demonstrated IC50 value of 81±2 nM and 97±2 nM, respectively.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.016
       
  • Phytochemicals with NO inhibitory effects and interactions with iNOS
           protein from Trigonostemon howii
    • Authors: Jun Ma; Xueyuan Yang; Peixia Wang; Bangjian Dong; Guochen Su; Muhetaer Tuerhong; Da-Qing Jin; Jing Xu; Dongho Lee; Yasushi Ohizumi; Jianping Lin; Yuanqiang Guo
      Abstract: Publication date: Available online 24 August 2017
      Source:Bioorganic Chemistry
      Author(s): Jun Ma, Xueyuan Yang, Peixia Wang, Bangjian Dong, Guochen Su, Muhetaer Tuerhong, Da-Qing Jin, Jing Xu, Dongho Lee, Yasushi Ohizumi, Jianping Lin, Yuanqiang Guo
      A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1−3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.
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      PubDate: 2017-09-02T11:58:05Z
      DOI: 10.1016/j.bioorg.2017.08.008
       
  • Novel dehydroabietylamine derivatives as potent inhibitors of
           acetylcholinesterase
    • Authors: Jana Wiemann; Anne Loesche; René Csuk
      Abstract: Publication date: Available online 1 August 2017
      Source:Bioorganic Chemistry
      Author(s): Jana Wiemann, Anne Loesche, René Csuk
      Nowadays, the inhibition of acetylcholinesterase is one of the main pharmacological strategies for the treatment of Alzheimer’s disease. Therefore, a set of thirty-four derivatives of the diterpenoid dehydroabietylamine has been synthesized and screened in colorimetric Ellman’s assays to determine their ability to inhibit the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). A systematic variation of the substitution of dehydroabietylamides enabled an approach to analogs showing a remarkable inhibition potency for AChE. Particularly N-benzoyldehydroabietylamines 11, 12 and 13 were excellent inhibitors for AChE, showing inhibition rates comparable to standard galantamine hydrobromide.
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      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.013
       
  • Design, synthesis and α-amylase inhibitory activity of novel chromone
           derivatives
    • Authors: P. Valentina; K. Ilango; Subhash Chander; Sankaranarayanan Murugesan
      Abstract: Publication date: Available online 1 August 2017
      Source:Bioorganic Chemistry
      Author(s): P. Valentina, K. Ilango, Subhash Chander, Sankaranarayanan Murugesan
      Quercetin is one of the naturally occurring polyphenol flavonoid predominantly known for antidiabetic activity. In the present study, by considering the structural requirements, twenty two novel chromone derivatives (5-26) as α-amylase inhibitor were designed and subsequently in-silico evaluated for drug likeness behaviour. Designed compounds were synthesized, characterized by spectral analysis and finally evaluated for the inhibition of α-amylase activity by in vitro assay. Tested compounds exhibited significant to weak activity with IC₅₀ range of 12-125 µM. Among the tested compounds, analogs 5, 8, 12, 13, 15, 17 and 22 exhibited significant human α-amylase inhibitory activity with IC₅₀ values < 25 µM, which can be further explored as anti-hyperglycemic agents. Putative binding mode of the significant and least active α-amylase inhibitors with the target enzyme was also explored by the docking studies.
      Graphical abstract image

      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.018
       
  • Design, synthesis and evaluation of newer
           5,6-dihydropyrimidine-2(1H)-thiones as GABA-AT inhibitors for
           anticonvulsant potential
    • Authors: Meeta Sahu; Nadeem Siddiqui; Ramsha Iqbal; Vidushi Sharma; Sharad Wakode
      Abstract: Publication date: Available online 28 July 2017
      Source:Bioorganic Chemistry
      Author(s): Meeta Sahu, Nadeem Siddiqui, Ramsha Iqbal, Vidushi Sharma, Sharad Wakode
      Several new 5,6-dihydropyrimidine-2(1H)-thione derivatives have been prepared and investigated for their potencies for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) test in mice. The acute neurotoxicity was measured by rotarod test. Compounds 3c and 3l were found active in both of the animal models. Further, in vitro GABA-AT enzyme activity assay was carried out to investigate the possible mechanism of action through GABA-AT inhibition. The most potent compounds 3c and 3l showed inhibitory potency (IC50) of 18.42 μM and 19.23 μM, respectively. The molecular modeling was performed for all the synthesized compounds. The docking results were found in concordant with the observed animal studies.
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      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.017
       
  • Exploration of aroyl/heteroaroyl iminothiazolines featuring
           2,4,5-trichlorophenyl moiety as a new class of potent, selective, and
           in-vitro efficacious glucosidase inhibitors
    • Authors: Madiha Kazmi; Sumera Zaib; Sayyeda Tayyeba Amjad; Imtiaz Khan; Aliya Ibrar; Aamer Saeed; Jamshed Iqbal
      Abstract: Publication date: Available online 25 July 2017
      Source:Bioorganic Chemistry
      Author(s): Madiha Kazmi, Sumera Zaib, Sayyeda Tayyeba Amjad, Imtiaz Khan, Aliya Ibrar, Aamer Saeed, Jamshed Iqbal
      A series of iminothiazolines (4a–j) featuring 2,4,5–trichlorophenyl moiety and aroyl/heteroaroyl substituents has been prepared from readily accessible thioureas. In-vitro screening against glucosidase enzymes showed highly specific inhibition of α-glucosidase with a marked dependence of the potency upon the nature of the aroyl/heteroaroyl substituents. The most potent representatives, bearing ortho-tolyl and bulky naphthyl groups displayed the highest inhibitory potential with IC50 value of 0.15 ± 0.01 µM compared to standard drug acarbose (IC50 = 38.2 ± 0.12 µM). Several other derivatives (4c, 4d, 4i and 4j) were also significantly powerful and selective inhibitors of α-glucosidase. Binding interactions of potent compounds 4b, 4c, 4h and 4i with α-glucosidase was explored by molecular docking simulation. These results clearly identified a new class of structural leads which can be further investigated for the development of promising α-glucosidase inhibitors for the prevention of diabetes mellitus.
      Graphical abstract image

      PubDate: 2017-08-02T14:56:14Z
      DOI: 10.1016/j.bioorg.2017.07.012
       
  • Issue TOC
    • Abstract: Publication date: August 2017
      Source:Bioorganic Chemistry, Volume 73


      PubDate: 2017-07-23T06:12:35Z
       
  • Synthesis and antioxidant ability of
           6,6’-diamino-6,6’-dideoxytrehalose
    • Authors: Wenqiang Tan; Qing Li; Tingting Zhou; Qiuhong Chen; Gang Wang; Fang Dong; Zhanyong Guo
      Abstract: Publication date: Available online 20 July 2017
      Source:Bioorganic Chemistry
      Author(s): Wenqiang Tan, Qing Li, Tingting Zhou, Qiuhong Chen, Gang Wang, Fang Dong, Zhanyong Guo
      In order to study the influence of amino group on antioxidant activity of oligosaccharides, an amino disaccharide, 6,6’-diamino-6,6’-dideoxytrehalose (DAMDT) was successfully prepared in this paper, and its antioxidant activities against DPPH, superoxide, hydrogen peroxide, and hydroxyl radicals, and reducing power were evaluated, respectively. The results indicated that DAMDT had better antioxidant activity than trehalose at any tested concentration. The influence of amino group on antioxidant activity of disaccharides is positive based on the results in this paper, and amination should be an effective method to improve the bioactivity of saccharides.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.005
       
  • Design, Synthesis, In Vitro Evaluation and Docking Studies on
           Dihydropyrimidine-Based Urease Inhibitors
    • Authors: Fatima Iftikhar; Yousaf Ali; Farooq Ahmad Kiani; Syed Fahad Hassan; Tabeer Fatima; Ajmal Khan; Basit Niaz; Abbas Hassan; Farzana Latif Ansari; Umer Rashid
      Abstract: Publication date: Available online 19 July 2017
      Source:Bioorganic Chemistry
      Author(s): Fatima Iftikhar, Yousaf Ali, Farooq Ahmad Kiani, Syed Fahad Hassan, Tabeer Fatima, Ajmal Khan, Basit Niaz, Abbas Hassan, Farzana Latif Ansari, Umer Rashid
      In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79 µM) and isatin Schiff base derivative 5a (0.23 µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.003
       
  • Synthesis and Anticancer Activity of New Thiazolo[3,2-a]Pyrimidines: DNA
           Binding and Molecular Modeling Study
    • Authors: Ghada S. Hassan; Shahenda M. El-Messery; Ahmad Abbas
      Abstract: Publication date: Available online 18 July 2017
      Source:Bioorganic Chemistry
      Author(s): Ghada S. Hassan, Shahenda M. El-Messery, Ahmad Abbas
      A novel series of nitrogenous heterocycles starting from chalcones including thiazolo[3,2-a]pyrimidines (20-67), were synthesized. Structure elucidation of the synthesized compounds was attained by the use of H1 NMR, C13 NMR, and Mass spectrometry. The obtained compounds were evaluated for their in-vitro anticancer activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Three cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and melanoma SK-MEL-2, exhibited some sensitivity against most of the tested compounds. Six compounds have passed the 5-log dose level NCI assay. Compounds 34 and 24 proved to be the most active derivatives with GI50, TGI, LC50 of 5.89, 20.0, 66.1% and 5.0, 19.5, 52.5% respectively. Compounds 36, 39, 63 showed lesser activity with GI50, TGI, LC50 3.2, 11.8, 38.9%, 3.4, 16.6, 60.3%, 3.5, 17.8, 66.1% respectively. DNA binding assay of synthesized compound were performed. Molecular docking showed that compounds 34, 42, and 60 could effectively fit into the minor groove and selectively bind with AT base pairs. The results could confer the anticancer activity of compounds 24, 34, 36, and 39 in vitro to their abilities to bind at DNA minor groove.
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      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.008
       
  • Synthesis, α-Glucosidase Inhibitory Activity and In Silico Study of
           Tris-Indole Hybrid Scaffold with Oxadiazole Ring: As Potential Leads for
           the Management of Type-II Diabetes Mellitus
    • Authors: Muhammad Taha; Fazal Rahim; Syahrul Imran; Nor Hadiani Ismail; Hayat Ullah; Manikandan Selvaraj; Muhammad Tariq Javid; Uzma Salar; Muhammad Ali; Khalid Mohammed Khan
      Abstract: Publication date: Available online 18 July 2017
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Fazal Rahim, Syahrul Imran, Nor Hadiani Ismail, Hayat Ullah, Manikandan Selvaraj, Muhammad Tariq Javid, Uzma Salar, Muhammad Ali, Khalid Mohammed Khan
      Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as 1H-NMR, EI-MS, and 13C-NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC50 = 2.00 ± 0.01-292.40 ± 3.16 μM as compared to standard acarbose (IC50 = 895.09 ± 2.04 µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.009
       
  • New Carbazole Linked 1,2,3-Triazoles as Highly Potent Non-sugar
           α-Glucosidase Inhibitors
    • Authors: Shazia Iqbal; Maria Aqeel Khan; Kulsoom Javaid; Rabia Sadiq; Saba Fazal-ur-Rehman; M. Iqbal Choudhary; Fatima Z. Basha
      Abstract: Publication date: Available online 16 July 2017
      Source:Bioorganic Chemistry
      Author(s): Shazia Iqbal, Maria Aqeel Khan, Kulsoom Javaid, Rabia Sadiq, Saba Fazal-ur-Rehman, M. Iqbal Choudhary, Fatima Z. Basha
      In the present study, a series of new carbazole linked 1H-1,2,3-triazoles (2-27) were synthesized via click reaction of N-propargyl-9H-carbazole (1) and azides of appropriate acetophenones and heterocycles. Synthesized carbazole triazoles including 7, 9, 10, 19, 20, and 23-26 (IC50 = 0.8 ± 0.01-100.8 ± 3.6 μM), exhibited several folds more potent α-glucosidase inhibitory in vitro activity as compared to standard drug, acarbose. Compounds 2-5, 7-13, and 17-27 did not show any cytotoxicity against 3T3 cell lines, except triazoles 6, and 14-16. Among the series, carbazole triazoles 23 (IC50 = 1.0 ± 0.057 μM) and 25 (IC50 = 0.8 ± 0.01 μM) were found to be most active, and could serve as an attractive building block in the search of new non-sugar derivatives as anti-diabetic agents.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.006
       
  • Design, synthesis and biological evaluation of some novel benzothiazole/
           benzoxazole and/ or benzimidazole derivatives incorporating a pyrazole
           scaffold as antiproliferative agents
    • Authors: Mohamed A. Abdelgawad; Rania B. Bakr; Hany A. Omar
      Abstract: Publication date: Available online 15 July 2017
      Source:Bioorganic Chemistry
      Author(s): Mohamed A. Abdelgawad, Rania B. Bakr, Hany A. Omar
      In an aim at developing new antiproliferative agents, new series of benzothiazole/ benzoxazole and/ or benzimidazole substituted pyrazole derivatives 11a-c, 12a-c and 13a-c were prepared and evaluated for their antiproliferative activity against breast carcinoma (MCF-7) and non-small cell lung cancer (A549) cell lines. The target compound, 2-acetyl-4-[(3-(1H-benzimidazol-2-yl)-phenyl]-hydrazono-5-methyl-2,4-dihydropyrazol-3-one (12a) was the most active compound against both MCF-7 and A549 cell lines with half maximal inhibitory concentrations (IC50) = 6.42 and 8.46 μM, respectively. Furthermore, the inhibitory activity of the all the target compounds against COX enzymes was recorded as a proposed mechanism for their antiproliferative activity. The obtained results revealed that the benzothiazolopyrazolone derivative 13c was the most potent COX-2 inhibitor (IC50 = 0.10 μM), while the 5-acetylbenzimidazolylpyrazolone derivative 12a was the most COX-2 selective (S.I. = 104.67) in comparison with celecoxib (COX-2 IC50 = 1.11 μM, S.I. = 13.33). Docking simulation on the most active compounds 12a and 13c had been performed to investigate the binding interaction of these active compounds within the binding site of COX-2 enzyme.Collectively, this work demonstrated the promising activity of the newly designed compounds as leads for further development into antiproliferative agents.
      Graphical abstract image

      PubDate: 2017-07-23T06:12:35Z
      DOI: 10.1016/j.bioorg.2017.07.007
       
  • New 1,3,4-Oxadiazole/Oxime hybrids: Design, Synthesis, anti-inflammatory,
           COX inhibitory activities and Ulcerogenic liability.
    • Authors: Heba S. Abd-Ellah; Mohamed Abdel-Aziz; Mai E. Shoman; Eman A.M. Beshr; TamerS. Kaoud; Al-Shaimaa F.F. Ahmed
      Abstract: Publication date: Available online 15 June 2017
      Source:Bioorganic Chemistry
      Author(s): Heba S. Abd-Ellah, Mohamed Abdel-Aziz, Mai E. Shoman, Eman A.M. Beshr, TamerS. Kaoud, Al-Shaimaa F.F. Ahmed
      A series of new 1,3,4-oxadiazole/oxime hybrids were synthesized and designed as potent COX inhibitors. The prepared compounds were evaluated for their anti-inflammatory, antioxidant and ulcerogenic activities. The results indicated that the prepared compounds exhibited remarkable anti-inflammatory activity with (69.60- 109.60% of indomethacin activity) after 4h. In vitro COX inhibitory assay showed that compounds 6d and 7h are potent COX inhibitors with IC50 of (1.10-0.94) and (2.30-5.00) µM on both COX-1 and COX-2 respectively. Compound 7h was found to inhibit both COXs non-competitively with Ki values of 73 µM and 89 µM. Most of the tested compounds showed ulcer-free stomachs compared to indomethacin.
      Graphical abstract image

      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.003
       
  • Hetarylcoumarins: Synthesis and biological evaluation as potent
           α-glucosidase inhibitors
    • Authors: Faryal Chaudhry; Shahnaz Choudhry; Rahila Huma; Muhammad Ashraf; Mariya al-Rashida; Rubina Munir; Ramsha Sohail; Bakhat Jahan; Munawar Ali Munawar; Misbahul Ain Khan
      Abstract: Publication date: Available online 10 May 2017
      Source:Bioorganic Chemistry
      Author(s): Faryal Chaudhry, Shahnaz Choudhry, Rahila Huma, Muhammad Ashraf, Mariya al-Rashida, Rubina Munir, Ramsha Sohail, Bakhat Jahan, Munawar Ali Munawar, Misbahul Ain Khan
      In search of better α-glucosidase inhibitors, a series of novel hetarylcoumarins (3a-3j) were designed and synthesized through a facile multicomponent route where p-toluenesulfonic acid (PTSA) was explored as an efficient catalyst. These new scaffolds were further evaluated for their α-glucosidase inhibition potentials. All the derivatives exhibited good to excellent results which were comparable or even better than of standard drug acarbose. Of these compounds, a dihalogenated compound 3f was found to be the most effective one with IC50: 2.53 ± 0.002 µM. Molecular docking has predicted the plausible binding interactions of compounds 3f, 3g and 3j with α-glucosidase.
      Graphical abstract image

      PubDate: 2017-05-12T09:14:12Z
      DOI: 10.1016/j.bioorg.2017.05.009
       
  • Structure-based Rational Design of Self-inhibitory Peptides to Disrupt the
           Intermolecular Interaction between the Troponin Subunits C and I in
           Neuropathic Pain
    • Authors: Junmin Yu; Shilei Wang; Junjie Yu; Chuansheng Liu; Fenghe Xu; Shijie Wang; Yusheng Yi; Yanwei Yin
      Abstract: Publication date: Available online 3 May 2017
      Source:Bioorganic Chemistry
      Author(s): Junmin Yu, Shilei Wang, Junjie Yu, Chuansheng Liu, Fenghe Xu, Shijie Wang, Yusheng Yi, Yanwei Yin
      The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC–TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders. Molecular dynamics simulation and binding free energy analysis suggests that the switch peptide can interact with TnC in a structurally and energetically independent manner. Terminal truncation of the peptide results in a number of potent TnC binders with considerably simplified structure and moderately decreased activity relative to the native switch. We also employ fluorescence polarization assays to substantiate the computational findings; it is found that the rationally designed peptides exhibit moderate or high affinity to TnC with dissociation constants K D at micromolar level.
      Graphical abstract image

      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.004
       
 
 
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