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  Subjects -> CHEMISTRY (Total: 871 journals)
    - ANALYTICAL CHEMISTRY (54 journals)
    - CHEMISTRY (610 journals)
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CHEMISTRY (610 journals)                  1 2 3 4 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 13)
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: 42)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 20)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 20)
ACS Macro Letters     Full-text available via subscription   (Followers: 25)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 40)
ACS Nano     Full-text available via subscription   (Followers: 266)
ACS Photonics     Full-text available via subscription   (Followers: 13)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 23)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chimica Slovenica     Open Access  
Acta Chromatographica     Full-text available via subscription   (Followers: 8)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 6)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 8)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 54)
Advanced Science Focus     Free   (Followers: 5)
Advances in Chemical Engineering and Science     Open Access   (Followers: 64)
Advances in Chemical Science     Open Access   (Followers: 15)
Advances in Chemistry     Open Access   (Followers: 20)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 25)
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: 43)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6)
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: 3)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 61)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 15)
American Journal of Chemistry     Open Access   (Followers: 29)
American Journal of Plant Physiology     Open Access   (Followers: 11)
American Mineralogist     Hybrid Journal   (Followers: 15)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 166)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 237)
Annales UMCS, Chemia     Open Access  
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 5)
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: 9)
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: 13)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal   (Followers: 1)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 8)
Applied Spectroscopy     Full-text available via subscription   (Followers: 22)
Applied Surface Science     Hybrid Journal   (Followers: 31)
Arabian Journal of Chemistry     Open Access   (Followers: 5)
ARKIVOC     Open Access   (Followers: 1)
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  
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 337)
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: 20)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 7)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 122)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 84)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 2)
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: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 6)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 71)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 7)
Catalysis Science and Technology     Free   (Followers: 8)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 9)
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: 17)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 73)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 26)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 22)
Chemical Reviews     Full-text available via subscription   (Followers: 183)
Chemical Science     Open Access   (Followers: 23)
Chemical Technology     Open Access   (Followers: 21)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 7)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 56)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 24)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Biology     Full-text available via subscription   (Followers: 32)
Chemistry & Industry     Hybrid Journal   (Followers: 6)
Chemistry - A European Journal     Hybrid Journal   (Followers: 153)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 16)
Chemistry and Materials Research     Open Access   (Followers: 20)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 247)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 19)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 1)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 14)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 11)
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: 11)
Chromatographia     Hybrid Journal   (Followers: 24)
Chromatography     Open Access   (Followers: 2)
Chromatography Research International     Open Access   (Followers: 6)
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: 11)
Colloids and Interfaces     Open Access  
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 6)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 5)
Combustion Science and Technology     Hybrid Journal   (Followers: 22)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 7)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 1)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 11)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 10)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Corrosion Series     Full-text available via subscription   (Followers: 6)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Croatica Chemica Acta     Open Access  
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Chromatography     Hybrid Journal  
Current Green Chemistry     Hybrid Journal  
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Microwave Chemistry     Hybrid Journal  
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 14)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 70)
Current Trends in Biotechnology and Chemical Research     Open Access   (Followers: 3)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  

        1 2 3 4 | 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  [3175 journals]
  • Synthesis of N′-phenyl-N-hydroxyureas and investigation of their
           inhibitory activities on human carbonic anhydrases
    • Authors: Murat Bozdag; Fabrizio Carta; Andrea Angeli; Sameh M. Osman; Fatmah A.S. Alasmary; Zeid AlOthman; Claudiu T. Supuran
      Pages: 1 - 6
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Murat Bozdag, Fabrizio Carta, Andrea Angeli, Sameh M. Osman, Fatmah A.S. Alasmary, Zeid AlOthman, Claudiu T. Supuran
      A series of N′-phenyl-N-hydroxyureas has been prepared by reacting hydroxylamine with aromatic isocyanates. These compounds were investigated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1), considering four physiologically relevant isoforms, the cytosolic isoforms hCA I and II, and tumor associated, transmembrane isoforms hCA IX and XII. The new compounds reported here did not inhibit the widespread cytosolic isoforms hCA I and II, but they inhibited the tumor associated isoforms with interesting potencies. The most effective inhibitors showed KIs ranging between 72.8 and 78.9 nM against hCA IX and between 6.9 and 7.2 against hCA XII, making them of interest as candidates for antitumor studies.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.029
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis and biological activity of
           4-(4-benzyloxy)phenoxypiperidines as selective and reversible LSD1
           inhibitors
    • Authors: Jiayue Xi; Siyuan Xu; Lulu Zhang; Xueyuan Bi; Yanshen Ren; Yu-Chih Liu; Yueqing Gu; Yungen Xu; Fei Lan; Xiaoming Zha
      Pages: 7 - 16
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Jiayue Xi, Siyuan Xu, Lulu Zhang, Xueyuan Bi, Yanshen Ren, Yu-Chih Liu, Yueqing Gu, Yungen Xu, Fei Lan, Xiaoming Zha
      Lysine specific demethylase 1 (LSD1) plays a vital role in epigenetic regulation of gene activation and repression in several human cancers and is recognized as a promising antitumor therapeutic target. In this paper, a series of 4-(4-benzyloxy)phenoxypiperidines were synthesized and evaluated. Among the tested compounds, compound 10d exhibited the potent and reversible inhibitory activity against LSD1 in vitro (IC50 = 4 μM). Molecular docking was conducted to predict its binding mode. Furthermore, 10d displayed it could inhibit migration of HCT-116 colon cancer cells and A549 lung cancer cells. Taken together, 10d deserves further investigation as a hit-to-lead for the treatment of LSD1 associated tumors.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.016
      Issue No: Vol. 78 (2018)
       
  • Synthesis, molecular docking study and thymidine phosphorylase inhibitory
           activity of 3-formylcoumarin derivatives
    • Authors: Muhammad Taha; Syed Adnan Ali Shah; Muhammad Afifi; Syahrul Imran; Sadia Sultan; Fazal Rahim; Nor Hadiani Ismail; Khalid Mohammed Khan
      Pages: 17 - 23
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Muhammad Taha, Syed Adnan Ali Shah, Muhammad Afifi, Syahrul Imran, Sadia Sultan, Fazal Rahim, Nor Hadiani Ismail, Khalid Mohammed Khan
      Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1–17) were synthesized, characterized by 1HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC50 values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC50 value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.028
      Issue No: Vol. 78 (2018)
       
  • Potential antioxidant activity of Morita-Baylis-Hillman adducts
    • Authors: Haitham Elleuch; Wafa Mihoubi; Mohamed Mihoubi; Emna Ketata; Ali Gargouri; Farhat Rezgui
      Pages: 24 - 28
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Haitham Elleuch, Wafa Mihoubi, Mohamed Mihoubi, Emna Ketata, Ali Gargouri, Farhat Rezgui
      The wide variety of potent biological activities of Morita-Baylis-Hillman adducts (MBH) encouraged us to synthesize new series of products belonging to this class of compounds, possessing different functionalities and exhibiting potential antioxidant activity. As part of our on-going program on targeting molecules with antioxidant activity, we describe herein different DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activities of MBH alcohols and their derivatives including acetates, phosphonates and hydrazonophosphonates. The obtained results showed that the strongest DPPH radical scavenging activity was observed in the case of hydrazonophosphonates in comparison to the other MBH derivatives.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.004
      Issue No: Vol. 78 (2018)
       
  • Novel carbamate derivatives as selective butyrylcholinesterase inhibitors
    • Authors: Marek Bajda; Kamil Łątka; Michalina Hebda; Jakub Jończyk; Barbara Malawska
      Pages: 29 - 38
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Marek Bajda, Kamil Łątka, Michalina Hebda, Jakub Jończyk, Barbara Malawska
      Selective butyrylcholinesterase inhibitors could be the promising drug candidates, used in treatment of Alzheimer's disease. The study describes the synthesis and biological activity of novel carbamate derivatives with N-phenylpiperazine, N-benzylpiperazine and 4-benzylpiperidine moieties. Biological studies revealed that most of these compounds displayed significant activity against BuChE. Compound 16 (3-(4-phenyl-piperazin-1-ylmethyl)-phenyl phenylcarbamate) turned out to be the most active (IC50 = 2.00 μM for BuChE). For all synthesized compounds lipophilicity and other physicochemical properties were calculated using computer programs. Relationship between these properties and activity was also checked. Binding mode with enzyme and the ensuing differences in activity were explained by the molecular modeling studies.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.003
      Issue No: Vol. 78 (2018)
       
  • Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B)
           inhibition from Cratoxylum cochinchinense
    • Authors: Zuo Peng Li; Hyeong-Hwan Lee; Zia Uddin; Yeong Hun Song; Ki Hun Park
      Pages: 39 - 45
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Zuo Peng Li, Hyeong-Hwan Lee, Zia Uddin, Yeong Hun Song, Ki Hun Park
      Four new caged xanthones (1–4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1–6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1–6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC50 values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining K m, V max, and the ratio of K ik and K iv, which revealed that all the compounds behaved as competitive inhibitors.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.026
      Issue No: Vol. 78 (2018)
       
  • Curcumin analogue
           1,5-bis(4-hydroxy-3-((4-methylpiperazin-1-yl)methyl)phenyl)penta-1,4-dien-3-one
           mediates growth arrest and apoptosis by targeting the PI3K/AKT/mTOR and
           PKC-theta signaling pathways in human breast carcinoma cells
    • Authors: Gamal Badr; Halise Inci Gul; Cem Yamali; Amal A.M. Mohamed; Badr M. Badr; Mustafa Gul; Ahmad Abo Markeb; Nagwa Abo El-Maali
      Pages: 46 - 57
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Gamal Badr, Halise Inci Gul, Cem Yamali, Amal A.M. Mohamed, Badr M. Badr, Mustafa Gul, Ahmad Abo Markeb, Nagwa Abo El-Maali
      Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of curcumin analogue J1 in these cancer cell lines were determined to be 5 ng/ml and 10 ng/ml, in MDA-MB-231 and MCF-7 cells respectively. Interestingly, at these concentrations, the J1 did not affect the viability of non-tumorigenic normal breast epithelial cells MCF-10. Furthermore, we found that J1 strongly induced growth arrest of these cancer cells by modulating the mitochondrial membrane potentials without significant effect on normal MCF-10 cells using JC-1 staining and flow cytometry analysis. Using annexin-V/PI double staining assay followed by flow cytometry analysis, we found that J1 robustly enhanced the induction of apoptosis by increasing the activity of caspases in MDA-MB-231 and MCF-7 cancer cells. In addition, treatment of breast cancer cells with J1 revealed that, in contrast to the expression of cyclin B1, this curcumin analogue vigorously decreased the expression of cyclin A, CDK2 and cyclin E and subsequently sensitized tumor cells to cell cycle arrest. Most importantly, the phosphorylation of AKT, mTOR and PKC-theta in J1-treated cancer cells was markedly decreased and hence affecting the survival of these cancer cells. Most interestingly, J1-treated cancer cells exhibited a significant inhibition in the activation of RhoA followed by reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal the therapeutic potential of the curcumin analogue J1 and the underlying mechanisms to fight breast cancer cells.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.006
      Issue No: Vol. 78 (2018)
       
  • Synthesis, molecular docking study and in vitro thymidine phosphorylase
           inhibitory potential of oxadiazole derivatives
    • Authors: Hayat Ullah; Fazal Rahim; Muhammad Taha; Imad Uddin; Abdul Wadood; Syed Adnan Ali Shah; Rai Khalid Farooq; Mohsan Nawaz; Zainul Wahab; Khalid Mohammed Khan
      Pages: 58 - 67
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Hayat Ullah, Fazal Rahim, Muhammad Taha, Imad Uddin, Abdul Wadood, Syed Adnan Ali Shah, Rai Khalid Farooq, Mohsan Nawaz, Zainul Wahab, Khalid Mohammed Khan
      We have synthesized oxadiazole derivatives (1–16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.020
      Issue No: Vol. 78 (2018)
       
  • Experimental and computational modeling of interaction of
           kolaviron-kolaflavanone with aldehyde dehydrogenase
    • Authors: Adejoke N. Kolawole; Valentine T. Akinladejo; Olusola O. Elekofehinti; Afolabi C. Akinmoladun; Ayodele O. Kolawole
      Pages: 68 - 79
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Adejoke N. Kolawole, Valentine T. Akinladejo, Olusola O. Elekofehinti, Afolabi C. Akinmoladun, Ayodele O. Kolawole
      Aldehyde dehydrogenases (ALDHs) are a diverse family of enzymes that catalyze the NAD(P)+-dependent detoxification of toxic aldehyde compounds. ALDHs are also involved in non-enzymatic ligand binding to endobiotics and xenobiotics. Here, the enzyme crucial non-canonical and non-catalytic interaction with kolaflavanone, a component of kolaviron, and a major bioflavonoid isolated from Garcinia kola (Bitter kola) was characterized by various spectroscopic and in silico approaches under simulated physiological condition. Kolaflavanone quenched the intrinsic fluorescence of ALDH in a concentration dependent manner with an effective quenching constant (K sv) of 1.14 × 103 L.mol−1 at 25 °C. The enzyme has one binding site for kolaflavanone with a binding constant (K a) of 2.57 × 104 L.mol−1 and effective Forster resonance energy transfer (FRET) of 4.87 nm. The bonding process was enthalpically driven. The reaction was not spontaneous and was predominantly characterized by Van der Waals forces and hydrogen bond. The flavonoid bonding slightly perturbed the secondary and tertiary structures of ALDH that was ‘tryptophan-gated’. The interaction was regulated by both diffusion and ionic strength. Molecular docking showed the binding of kolaflavanone was at the active site of ALDH and the participation of some amino acid residues in the complex formation with −9.6 kcal mol−1 binding energy. The profiles of atomic fluctuations indicated the rigidity of the ligand-binding site during the simulation. With these, ALDH as a subtle nano-particle determinant of kolaviron bioavailability and efficacy is hereby proposed.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.012
      Issue No: Vol. 78 (2018)
       
  • Novel N-substituted 5-aminosalicylamides as dual inhibitors of
           cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological
           evaluation and docking study
    • Authors: Mohamed K.S. El-Nagar; Hajjaj H.M. Abdu-Allah; Ola I.A. Salem; Abdel-Hamid N. Kafafy; Hanan S.M. Farghaly
      Pages: 80 - 93
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Mohamed K.S. El-Nagar, Hajjaj H.M. Abdu-Allah, Ola I.A. Salem, Abdel-Hamid N. Kafafy, Hanan S.M. Farghaly
      Three new series of 5-aminosalicylic acid derivatives; series I (14, 16–18), series II (19–30) and series III (31–41) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval. Selected derivatives were evaluated in vitro to inhibit ovine COX-1, human recombinant COX-2 and 5-LOX enzymes. Compounds 34 & 35 exhibited significant COX-2 inhibition (IC50 = 0.10 µM) with significant COX-2 selectivity indices (SI = 135 & 145 respectively) approximate to celecoxib (IC50 = 0.049 µM, SI = 308.16) and exceeding indomethacin (IC50 = 0.51 µM, SI = 0.08). Interestingly, all compounds showed superior 5-LOX inhibitory activity about 2–5 times relative to zileuton. Compound 16 was the superlative 5-LOX inhibitor that revealed (IC50 = 3.41 µM) relative to zileuton (IC50 = 15.6 µM). Compounds 34, 35, 36 and 41 showed significant dual COX-2/5-LOX inhibitions. The gastric ulcerogenic effect of compound 36 was examined on gastric mucosa of albino rats and they showed superior GI safety profile compared with indomethacin. Molecular docking studies of the compounds into the binding sites of COX-1, COX-2 and 5-LOX allowed us to shed light on the binding mode of these novels dual COX and 5-LOX inhibitors.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.023
      Issue No: Vol. 78 (2018)
       
  • Synthesis of some novel orcinol based coumarin triazole hybrids with
           capabilities to inhibit RANKL-induced osteoclastogenesis through NF-κB
           signaling pathway
    • Authors: Boddu Rama Krishna; Dinesh Thummuri; V.G.M. Naidu; Sistla Ramakrishna; Uppuluri Venkata Mallavadhani
      Pages: 94 - 102
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Boddu Rama Krishna, Dinesh Thummuri, V.G.M. Naidu, Sistla Ramakrishna, Uppuluri Venkata Mallavadhani
      A total of twenty-two novel coumarin triazole hybrids (4a-4k and 6a-6k) were synthesized from orcinol in good to excellent yields of 70–94%. The structures of all the synthesized compounds were elucidated by spectroscopic techniques such as 1H NMR, 13C NMR, and HRMS. The anti-inflammatory potential of synthesized compounds was investigated against the proinflammatory cytokine, TNF-α on U937 cell line and compounds 4d, 4j, and 6j were found to exhibit promising anti-inflammatory activity. These three compounds were further screened against TNF-α on LPS-stimulated RAW 264.7 cells, which confirm their anti-inflammatory potential. Furthermore, the above said active compounds were tested for their inhibitory effect on RANKL-induced osteoclastogenesis in RAW 264.7 cells by using tartrate resistant acid phosphatase (TRAP) staining assay at 10 µM. Molecular mechanism studies demonstrated that compound 4d exhibited dose dependent inhibition of RANKL-induced osteoclastogenesis by suppression of the NF-kB pathway. Thus, compound 4d is a promising candidate for further optimization to develop as a potent anti-osteoporotic agent.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.005
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis, analgesic, anti-inflammatory activity of novel
           pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of
           COX-2/5-LOX enzymes: Histopathological and docking studies
    • Authors: Mohamed A. Abdelgawad; Madlen B. Labib; Waleed A.M. Ali; Gehan Kamel; Amany A. Azouz; EL-Shaymaa EL-Nahass
      Pages: 103 - 114
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Mohamed A. Abdelgawad, Madlen B. Labib, Waleed A.M. Ali, Gehan Kamel, Amany A. Azouz, EL-Shaymaa EL-Nahass
      A series of newly synthesized 4-aryl-hydrazonopyrazolones were designed and their structures were confirmed by spectral and elemental analyses. All synthesized compounds were evaluated for their in vitro COXs, 5-LOX inhibition, in vivo analgesic and anti-inflammatory activities. Compounds 5d, 5f and 5i were found to be the most potent COX-2/5-LOX inhibitors with superior COX-2 selectivity index values (SI = 5.29–5.69) to reference standard celecoxib (SI = 3.52). Four compounds; 5b, 5c, 5d and 5f showed excellent anti-inflammatory activity (% edema inhibition = 72.72–54.54%) and perfect ED50 values (ED50 = 0.044–0.104 mmol/kg) relative to celecoxib (ED50 = 0.032 mmol/kg). To explore the most active compounds, ulcerogenic effect on stomach in comparison with indomethacin and celecoxib in addition to histopathological investigations were performed. Compound 5f showed better gastric profile (UI = 2.33) than celecoxib (UI = 3.00). Also, 5f caused 50% increase in thermal pain threshold close to reference drug indomethacin (53.13%). Docking study of all the target compounds into COX-2 and 5-LOX active sites was performed to rational their anti-inflammatory activities.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.011
      Issue No: Vol. 78 (2018)
       
  • Antimicrobial effects of N-benzyloxycarbonyl-S-(2,4-dinitrophenyl)
           glutathione diesters against chloroquinine sensitive (NF54) and resistant
           (K1) strains of Plasmodium falciparum
    • Authors: Sylvie Daunes; Claudius D'Silva
      Pages: 115 - 118
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Sylvie Daunes, Claudius D'Silva
      N-Benzyloxycarbony-S-(2,4-dinitrophenyl)glutathione diesters have been investigated for antimalarial activity against chloroquinine sensitive (NF54) and resistant (K1) strains of P. falciparum. Both strains appear equally susceptible to inhibition by compounds 1–4, with an IC50 ∼ 4.92–6.97 μM, consistent with the target of these compounds being the PfMRP transporter. Against the NF54 strain, diester derivatives containing ethyl side chains showed lower in vitro activity than those with methyl side chains 1–4, IC50 ∼ 5.7–6.97 μM with the exception of compound 5 (IC50 > 25 μM). The cytotoxicity of compounds with log P ∼ 3.9–5.8 were lower against the murine L6 cell line than compounds with a higher log P > 5.8 that were toxic. Overall the cytotoxicity of compounds 1–7 were lower against KB cells than against the L6 cell line with the exception of compound 4, which showed a higher relative toxicity.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.008
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis, in vivo and in silico evaluation of phenacyl triazole
           hydrazones as new anticonvulsant agents
    • Authors: Leila Dehestani; Nematollah Ahangar; Seyedeh Mahdieh Hashemi; Hamid Irannejad; Patrick Honarchian Masihi; Aidin Shakiba; Saeed Emami
      Pages: 119 - 129
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Leila Dehestani, Nematollah Ahangar, Seyedeh Mahdieh Hashemi, Hamid Irannejad, Patrick Honarchian Masihi, Aidin Shakiba, Saeed Emami
      A series of phenacyl triazole hydrazones 3 have been designed based on the hybridization of (arylalkly)triazole and aroyl hydrazone scaffolds as new anticonvulsant agents. The target compounds 3 were easily synthesized from appropriate phenacyl triazoles and aryl acid hydrazides and characterized by IR, NMR and Mass spectroscopy. The in vivo anticonvulsant evaluation of synthesized compounds by using MES and PTZ tests revealed that they are more effective in MES model respect to PTZ test. All compounds showed 33–100% protection against MES-induced seizures at the dose of 100 mg/kg. However, the isonicotinic acid hydrazide derivative 3h showed the best profile of activity in both models. Molecular docking studies of compound 3h with different targets (NMDA, AMPA, GABAA and sodium channel), postulated that the compound acts mainly via GABAA receptors. In silico molecular properties predictions indicated that all compounds have favourable oral bioavailability and BBB permeability.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.001
      Issue No: Vol. 78 (2018)
       
  • Synthesis and biological evaluation of pyrimidine bridged combretastatin
           derivatives as potential anticancer agents and mechanistic studies
    • Authors: Bhupinder Kumar; Praveen Sharma; Vivek Prakash Gupta; Madhu Khullar; Sandeep Singh; Nilambra Dogra; Vinod Kumar
      Pages: 130 - 140
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Bhupinder Kumar, Praveen Sharma, Vivek Prakash Gupta, Madhu Khullar, Sandeep Singh, Nilambra Dogra, Vinod Kumar
      A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC50 values of 4.67 µM & 3.38 µM and 4.63 µM & 3.71 µM against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity (in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a, was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.027
      Issue No: Vol. 78 (2018)
       
  • Synthesis, molecular modelling and biological evaluation of
           tetrasubstituted thiazoles towards cholinesterase enzymes and cytotoxicity
           studies
    • Authors: Amara Mumtaz; Muhammad Shoaib; Sumera Zaib; Muhammad Shakil Shah; Huma Aslam Bhatti; Aamer Saeed; Izhar Hussain; Jamshed Iqbal
      Pages: 141 - 148
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Amara Mumtaz, Muhammad Shoaib, Sumera Zaib, Muhammad Shakil Shah, Huma Aslam Bhatti, Aamer Saeed, Izhar Hussain, Jamshed Iqbal
      Alzheimer is a neurodegenerative disease and requires the development of new scaffold to treat it. In this regard, thiazoles derivative are playing their significant role. In the current research paper we have focused our attention for the development of tetrasubstituted thiazole (3a-h) derivatives using domino synthesis by mixing the thiourea as a precursor, with acetophenone in the presence of iodine and tosic acid in DMSO and refluxed for 12–22 h. The structures of the newly synthesized compounds were confirmed by FTIR, 1H NMR, 13C NMR and EIMS analysis. Thiazole derivatives were analyzed for their biological significances against acetyl and butylcholinesterase enzymes and compound 3b and 3d were found more active against these enzyme, respectively. The mode of inhibition was determined for the potent compounds against both the enzymes. Moreover, the molecular docking studies were carried out to explore the interactive behavior of the compounds within the active pocket of enzymes. Furthermore, the derivatives (3a-h) were evaluated for their anticancer potential against HeLa cancer cell lines. Most potent inhibition was observed by compound 3b.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.024
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis and biological evaluation of novel 1,3,4-trisubstituted
           pyrazole derivatives as potential chemotherapeutic agents for
           hepatocellular carcinoma
    • Authors: Marwa F. Harras; Rehab Sabour
      Pages: 149 - 157
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Marwa F. Harras, Rehab Sabour
      A series of novel 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their cytotoxic activity against three different cancer cell lines namely HCT116, UO-31 and HepG2. Compounds 3b, 3d, 7b and 9 showed excellent anticancer activity against all the tested cancer cell lines and had better cytotoxic activities than the reference drug, Sorafenib. Therefore, these compounds were chosen to be further evaluated in a panel of HCC cell lines. Among them, 3b and 7b were the most active compounds against HCC cells used here. Further studies on the mechanism demonstrated that 3b and 7b induced apoptosis in addition to induction of cell cycle arrest at G2/M phase in HepG2 and Huh7 cells. Consistent with these results, caspase-3 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases-3. In addition, CDK1 inhibition assay was done and it was found that compounds 3b and 7b inhibited CDK1 activities with IC50 values of 2.38 and 1.52 µM, respectively. Finally, pyrazole derivatives 3b and 7b showed potent bioactivities, indicating that these compounds could be potent anticancer drugs in the future.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.014
      Issue No: Vol. 78 (2018)
       
  • Synthesis of stable benzimidazole derivatives bearing pyrazole as
           anticancer and EGFR receptor inhibitors
    • Authors: Md. Jawaid Akhtar; Ahsan Ahmed Khan; Zulphikar Ali; Rikeshwer Prasad Dewangan; Md. Rafi; Md. Quamrul Hassan; Md. Sayeed Akhtar; Anees Ahmad Siddiqui; Sangh Partap; Santosh Pasha; M. Shahar Yar
      Pages: 158 - 169
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Md. Jawaid Akhtar, Ahsan Ahmed Khan, Zulphikar Ali, Rikeshwer Prasad Dewangan, Md. Rafi, Md. Quamrul Hassan, Md. Sayeed Akhtar, Anees Ahmad Siddiqui, Sangh Partap, Santosh Pasha, M. Shahar Yar
      A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC50 = 2.2 µM) and EGFR binding (IC50 = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = −34.581 Kcal/mol.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.002
      Issue No: Vol. 78 (2018)
       
  • N-linoleoylamino acids as chiral probes of substrate binding by soybean
           lipoxygenase-1
    • Authors: Charles H. Clapp; Justin Pachuski; Natasha F. Bassett; Kathleen A. Bishop; Gillian Carter; Megan Young; Thomas Young; Yuhan Fu
      Pages: 170 - 177
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Charles H. Clapp, Justin Pachuski, Natasha F. Bassett, Kathleen A. Bishop, Gillian Carter, Megan Young, Thomas Young, Yuhan Fu
      Lipoxygenases catalyze the oxygenation of polyunsaturated fatty acids and their derivatives to produce conjugated diene hydroperoxides. Soybean lipoxygenase-1 (SBLO-1) has been the subject of intensive structural and mechanistic study, but the manner in which this enzyme binds substrates is uncertain. Previous studies suggest that the fatty acyl group of the substrate binds in an internal cavity near the catalytic iron with the polar end at the surface of the protein or perhaps external to the protein. To test this model, we have investigated two pairs of enantiomeric N-linoleoylamino acids as substrates for SBLO-1. If the amino acid moiety binds external to the protein, the kinetics and product distribution should show little or no sensitivity to the stereochemical configuration of the amino acid moiety. Consistent with this expectation, N-linoleoyl-l-valine (LLV) and N-linoleoyl-d-valine (LDV) are both good substrates with kcat/Km values that are equal within error and about 40% higher than kcat/Km for linoleic acid. Experiments with N-linoleoyl-l-tryptophan (LLT) and N-linoleoyl-d-tryptophan (LDT) were complicated by the low critical micelle concentrations (CMC = 6–8 μM) of these substances. Below the CMC, LDT is a better substrate by a factor of 2.7. The rates of oxygenation of LDT and LLT continue to rise above the CMC, with modest stereoselectivity in favor of the d enantiomer. With all of the substrates tested, the major product is the 13(S)-hydroperoxide, and the distribution of minor products is not appreciably affected by the configuration of the amino acid moiety. The absence of stereoselectivity with LLV and LDV, the modest magnitude of the stereoselectivity with LLT and LDT, and the ability micellar forms of LLT and LDT to increase the concentration of available substrate are all consistent with the hypothesis that the amino acid moiety binds largely external to SBLO-1 and interacts with it only weakly.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.010
      Issue No: Vol. 78 (2018)
       
  • Application of α- and β-naphthoflavones as monooxygenase inhibitors of
           Absidia coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium
           sp. KCh 6651 in transformation of 17α-methyltestosterone
    • Authors: Tomasz Janeczko; Jarosław Popłoński; Ewa Kozłowska; Monika Dymarska; Ewa Huszcza; Edyta Kostrzewa-Susłow
      Pages: 178 - 184
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Tomasz Janeczko, Jarosław Popłoński, Ewa Kozłowska, Monika Dymarska, Ewa Huszcza, Edyta Kostrzewa-Susłow
      In this work, 17α-methyltestosterone was effectively hydroxylated by Absidia coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium sp. KCh 6651. A. coerulea KCh 93 afforded 6β-, 12β-, 7α-, 11α-, 15α-hydroxy derivatives with 44%, 29%, 6%, 5% and 9% yields, respectively. S. racemosum KCh 105 afforded 7α-, 15α- and 11α-hydroxy derivatives with yields of 45%, 19% and 17%, respectively. Chaetomium sp. KCh 6651 afforded 15α-, 11α-, 7α-, 6β-, 9α-, 14α-hydroxy and 6β,14α-dihydroxy derivatives with yields of 31%, 20%, 16%, 7%, 5%, 7% and 4%, respectively. 14α-Hydroxy and 6β,14α-dihydroxy derivatives were determined as new compounds. Effect of various sources of nitrogen and carbon in the media on biotransformations were tested, however did not affect the degree of substrate conversion or the composition of the products formed. The addition of α- or β-naphthoflavones inhibited 17α-methyltestosterone hydroxylation but did not change the percentage composition of the resulting products.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.021
      Issue No: Vol. 78 (2018)
       
  • Molecular docking studies and facile synthesis of most potent biologically
           active N-tert-butyl-4-(4-substituted
           phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide
           hybrids: An approach for microwave-assisted syntheses and biological
           evaluation
    • Authors: Rakesh R. Chavan; Kallappa M. Hosamani; Badarinath D. Kulkarni; Shrinivas D. Joshi
      Pages: 185 - 194
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Rakesh R. Chavan, Kallappa M. Hosamani, Badarinath D. Kulkarni, Shrinivas D. Joshi
      An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide derivatives (4a–4j) under microwave-irradiation has been described. All the newly synthesized compounds (4a–4j) were characterized by elemental analysis and spectroscopic studies. The synthesised compounds (4a–4j) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compound (4f) exhibits antibacterial effect with MIC–2.5 μg/mL against gram positive S. aureus bacterial strain compared to standard ciprofloxacin drug (MIC–10 μg/mL). The compound (4c) shows an inhibition of heat induced protein denaturation 75.42% at a concentration of 31.25 μg/ml and is almost ten times more active than compared to standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.007
      Issue No: Vol. 78 (2018)
       
  • Synthesis, biological evaluation, and docking studies of novel
           5,6-diaryl-1,2,4-triazine thiazole derivatives as a new class of
           α-glucosidase inhibitors
    • Authors: Guangcheng Wang; Zhiyun Peng; Zipeng Gong; Yongjun Li
      Pages: 195 - 200
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Guangcheng Wang, Zhiyun Peng, Zipeng Gong, Yongjun Li
      A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized and characterized by 1H NMR and 13C NMR and evaluated for their α-glucosidase inhibitory activity. All tested compounds displayed good α-glucosidase inhibitory activity with IC50 values ranging between 2.85 ± 0.13 and 14.19 ± 0.23 μM when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Compound 7i (IC50 = 2.85 ± 0.13 μM) exhibited the highest activity among this series of compounds. Molecular docking studies were carried out in order to investigate the binding mode of this class of compounds to α-glucosidase. This study showed that these 5,6-diaryl-1,2,4-triazine thiazole derivatives are a new class of α-glucosidase inhibitors.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.015
      Issue No: Vol. 78 (2018)
       
  • Synthesis, in vitro α-glucosidase inhibitory potential and molecular
           docking study of thiadiazole analogs
    • Authors: Muhammad Tariq Javid; Fazal Rahim; Muhammad Taha; Haseeb Ur Rehman; Mohsan Nawaz; Abdul wadood; Syahrul Imran; Imad Uddin; Ashik Mosaddik; Khalid Mohammed Khan
      Pages: 201 - 209
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Muhammad Tariq Javid, Fazal Rahim, Muhammad Taha, Haseeb Ur Rehman, Mohsan Nawaz, Abdul wadood, Syahrul Imran, Imad Uddin, Ashik Mosaddik, Khalid Mohammed Khan
      α-Glucosidase is a catabolic enzyme that regulates the body’s plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1–13) and 2-amino-thiadiazole based Schiff bases (14–22) were synthesized, characterized by 1H NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with IC50 values ranging between 2.30 ± 0.1 to 38.30 ± 0.7 μM, when compare with standard drug acarbose having IC50 value of 39.60 ± 0.70 μM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with IC50 values of 3.30 ± 0.1, 5.80 ± 0.2, 2.30 ± 0.1, 2.70 ± 0.1, 2.30 ± 0.1, 5.50 ± 0.1, 4.70 ± 0.2, and 5.50 ± 0.2 μM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for all compounds. The binding interactions of these compounds were confirmed through molecular docking.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.022
      Issue No: Vol. 78 (2018)
       
  • Chemoenzymatic synthesis of new derivatives of glycyrrhetinic acid with
           antiviral activity. Molecular docking study
    • Authors: M. Antonela Zígolo; Maximiliano Salinas; Laura Alché; Alicia Baldessari; Guadalupe García Liñares
      Pages: 210 - 219
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): M. Antonela Zígolo, Maximiliano Salinas, Laura Alché, Alicia Baldessari, Guadalupe García Liñares
      We present an efficient approach to the synthesis of a series of glycyrrhetinic acid derivatives. Six derivatives, five of them new compounds, were obtained through chemoenzymatic reactions in very good to excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile:substrate ratio, enzyme:substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. Moreover, in order to explain the reactivity of glycyrrhetinic acid and the acetylated derivative to different nucleophiles in the enzymatic reactions, molecular docking studies were carried out. In addition, one of the synthesized compounds exhibited remarkable antiviral activity against TK + and TK- strains of Herpes simplex virus type 1 (HSV-1), sensitive and resistant to acyclovir (ACV) treatment.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.018
      Issue No: Vol. 78 (2018)
       
  • Synthesis, anti-inflammatory screening, molecular docking, and
           COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives
    • Authors: Ibrahim Chaaban; Ola H. Rizk; Tamer M. Ibrahim; Shery S. Henen; El-Sayeda M. El-Khawass; Aida E. Bayad; Ibrahim M. El-Ashmawy; Hisham A. Nematalla
      Pages: 220 - 235
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Ibrahim Chaaban, Ola H. Rizk, Tamer M. Ibrahim, Shery S. Henen, El-Sayeda M. El-Khawass, Aida E. Bayad, Ibrahim M. El-Ashmawy, Hisham A. Nematalla
      New quinoline compounds comprising pyrazole scaffold through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a) were found to exhibit promising anti-inflammatory profiles in acute and sub-acute inflammatory models. They were screened for their ulcerogenic activity and none of them showed significant ulcerogenic activity comparable to the reference drug celecoxib and are well tolerated by experimental animals with high safety margin (ALD50 > 0.3 g/kg). Compounds 5c, 11b,c, 12c, 14a,b, 20a and 21a showed significant in vitro LOX inhibitory activity higher than that of zileuton. In vitro COX-1/COX-2 inhibition study revealed that compounds 12c, 14a,b and 20a showed higher selectivity towards COX-2 than COX-1. Among the tested compounds, 12c, 14a and 14b showed the highest inhibitory activity against COX-2 with an IC50 values of 0.1, 0.11 and 0.11 μM respectively. The docking experiments attempted to postulate the binding mode for the most active compounds in the binding site of COX-2 enzymes and confirmed the high selectivity binding towards COX-2 enzyme over COX-1.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.023
      Issue No: Vol. 78 (2018)
       
  • Conventional and microwave prompted synthesis, antioxidant,
           anticholinesterase activity screening and molecular docking studies of new
           quinolone-triazole hybrids
    • Authors: Arif Mermer; Neslihan Demirbaş; Yakup Şirin; Harun Uslu; Zeynep Özdemir; Ahmet Demirbaş
      Pages: 236 - 248
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Arif Mermer, Neslihan Demirbaş, Yakup Şirin, Harun Uslu, Zeynep Özdemir, Ahmet Demirbaş
      The synthesis of ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylates (4, 5) was performed via the reaction of corresponding anilines with diethyl ethoxymethylenemalonate under conventional and also microwave promoted conditions. The treatment of 4 and 5 afforded the corresponding hydrazides (6 and 7). These hydrazides were converted to the corresponding carbo(thio)amides (9a-f and 10a-e) which were then subjected to an intramolecular cyclisation leading to the formation of quinolone-triazole hybrids (11a-f and 12a-e). The newly synthesized compounds were screened for their biological activities such as antioxidant capacity (AC) and acetylcholinesterase Activity. Inhibition of cholinesterases is an effective method to curb Alzheimer’s disease, a progressive and fatal neurological disorder. A series of some novel quinolonederivatives were designed, synthesized, and their inhibitory effects on AChE were evaluated. We obtained our compounds and determined their anticholinesterase activities according to the Ellman’s method. 9b and 10c showed the best AChE inhibition with 0.48 ± 0.02 and 0.52 ± 0.07, respectively. Docking studies were performed for the most active compounds (9b, 10c) and interaction modes with enzyme active sites were determined. As a result of these studies, a strong interaction between these compounds and the active sites of AChE enzyme was revealed.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.017
      Issue No: Vol. 78 (2018)
       
  • Competitive neutrophil elastase inhibitory isoflavones from the roots of
           Flemingia philippinensis
    • Authors: Jeong Yoon Kim; Yan Wang; Zia Uddin; Yeong Hun Song; Zuo Peng Li; Janar Jenis; Ki Hun Park
      Pages: 249 - 257
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Jeong Yoon Kim, Yan Wang, Zia Uddin, Yeong Hun Song, Zuo Peng Li, Janar Jenis, Ki Hun Park
      Flemingia philippinensis has been used throughout history to cure rheumatism associated with neutrophil elastase (NE). In this study, we isolated sixteen NE inhibitory flavonoids (1–16), including the most potent and abundant prenyl isoflavones (1–9), from the F. philippinensis plant. These prenyl isoflavones (2, 3, 5, 7, and 9) competitively inhibited NE, with IC50 values of 1.3–12.0 μM. In addition, they were reversible, simple, slow-binding inhibitors according to their respective parameters. Representative compound 3 had an IC50 = 1.3 μM, k 3 = 0.04172 μM−1 min−1, k 4 = 0.0064 min−1, and K i app = 0.1534 μM. The K ik/K iv ratios (18.5 ∼ 24.6) for compound 3 were consistent with typical competitive inhibitors. The prenyl functionality of isoflavones significantly affected inhibitory potencies and mechanistic behavior by shifting the competitive mode to a noncompetitive one. The remaining flavonoids (10–16) were confirmed as mixed type I inhibitors that preferred to bind free enzyme rather than the enzyme-substrate complex. Fluorescence quenching analyses indicated that the inhibitory potency (IC50) closely followed the binding affinity (K SV).
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.024
      Issue No: Vol. 78 (2018)
       
  • Structure-based design, synthesis and evaluation of 2,4-diaminopyrimidine
           derivatives as novel caspase-1 inhibitors
    • Authors: Shivani Patel; Palmi Modi; Vishal Ranjan; Mahesh Chhabria
      Pages: 258 - 268
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Shivani Patel, Palmi Modi, Vishal Ranjan, Mahesh Chhabria
      Interleukin-1β converting enzyme contributes in various inflammatory and autoimmune diseases by maturing pro-inflammatory cytokines IL-1β, IL-18 and IL-33. Therefore, inhibition caspase-1 may provide a potential therapeutic strategy for the treatment of chronic inflammatory diseases. Here we have reported structure-based design, synthesis and biological evaluation of 2,4-diaminopyrimidine derivatives (6a-6w) as potential caspase-1 inhibitors. Six compounds 6m, 6n, 6o, 6p, 6q and 6r showed significant enzymatic inhibition with IC5 0 ranging from 0.022 to 0.078 µM. These compounds also displayed excellent cellular potency at sub-micromolar concentration. Moreover, molecular docking studies provided the useful binding insights specific for caspase-1 inhibition. All these results indicated that compounds 6m, 6n and 6o could be potential leads for the development of newer caspase-1 inhibitors as anti-inflammatory agents.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.019
      Issue No: Vol. 78 (2018)
       
  • Synthesis, and In Vitro and In Silico α-Glucosidase Inhibitory Studies of
           5-Chloro-2-Aryl Benzo[d]thiazoles
    • Authors: Shazia Shah; Arshia; Kulsoom Javaid; Humaira Zafar; Khalid Mohammed Khan; Ruqaiya Khalil; Zaheer Ul-Haq; Shahnaz Perveen; M. Iqbal Choudhary
      Pages: 269 - 279
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Shazia Shah, Arshia, Kulsoom Javaid, Humaira Zafar, Khalid Mohammed Khan, Ruqaiya Khalil, Zaheer Ul-Haq, Shahnaz Perveen, M. Iqbal Choudhary
      Twenty-five derivatives of 5-chloro-2-aryl benzo[d]thiazole (1–25) were synthesized and evaluated for their α-glucosidase (S. cerevisiae EC 3.2.1.20) inhibitory activity in vitro. Among them eight compounds showed potent activity with IC50 values between 22.1 ± 0.9 and 136.2 ± 5.7 μM, when compared with standard acarbose (IC50 = 840 ± 1.73 μM). The most potent compounds 4, 9, and 10 showed IC50 values in the range of 22.1 ± 0.9 to 25.6 ± 1.5 μM. Compounds 2, 5, 11, and 19 showed IC50 values within the range of 40.2 ± 0.5 to 60.9 ± 2.0 μM. Compounds 1 and 3 were also found to be good inhibitors with IC50 values 136.2 ± 5.7 and 104.8 ± 9.9 μM, respectively. Their activities were compared with α-glucosidase inhibitor drug acarbose (standard) (IC50 = 840 ± 1.73 μM). The remaining compounds were inactive. Structure-activity relationships (SAR) have also been established. Kinetics studies indicated compounds 2, 3, 10, 19, and 25 to be non-competitive, while 1, 5, 9, and 11 as competitive inhibitors of α-glucosidase enzyme. All the active compounds (1–5, 9–11, and 19) were also found to be non-cytotoxic, in comparison to the standard drug i.e., doxorubicin (IC50 = 0.80 ± 0.12 μM) in MTT assay. Furthermore, molecular interactions of active compounds with the enzyme binding sites were predicted through molecular modeling studies.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.02.013
      Issue No: Vol. 78 (2018)
       
  • Synthesis and characterization of new inhibitors of cholinesterases based
           on N-phenylcarbamates: In vitro study of inhibitory effect, type of
           inhibition, lipophilicity and molecular docking
    • Authors: Katarína Vorčáková; Magdaléna Májeková; Eva Horáková; Pavel Drabina; Miloš Sedlák; Šárka Štěpánková
      Pages: 280 - 289
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Katarína Vorčáková, Magdaléna Májeková, Eva Horáková, Pavel Drabina, Miloš Sedlák, Šárka Štěpánková
      Based on current treatment of Alzheimer's disease, where the carbamate inhibitor Rivastigmine is used, two series of carbamate derivatives were prepared: (i) N-phenylcarbamates with additional carbamate group (1–12) and (ii) N-phenylcarbamates with monosaccharide moiety (13–24). All compounds were tested for the inhibitory effect on both of the cholinesterases, electric eel acetylcholinesterase (eeAChE) and butyrylcholinesterase from equine serum (eqBChE) and the inhibitory activity (expressed as IC50 values) was compared with that of the established drugs Galanthamine and Rivastigmine. The compounds with two carbamate groups 1–12 revealed higher inhibitory efficiency on both cholinesterases in compared with monosaccharide derived carbamates 13–24 and with Rivastigmine. The significant decrease of inhibitory efficiency on eqBChE (also for eeAChE but in less manner) was observed after deacetalization of monosaccharide. Moreover, the type of inhibitory mechanism of five chosen compounds was studied. It was found, that compounds with two carbamate groups act presumably via a mixed inhibitory mechanism and the compounds with monosaccharide moiety act as non-competitive inhibitors. The lipophilicity of tested compounds was determined using partition coefficient. Specific positions of the inhibitors in the binding sites of cholinesterases were determined using molecular modeling and the results indicate the importance of phenylcarbamate orientation in the catalytic gorges of both enzymes.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.012
      Issue No: Vol. 78 (2018)
       
  • Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and
           autophagy pathways and their carbonic anhydrase inhibitory effects on hCA
           I, hCA II, hCA IX, hCA XII isoenzymes
    • Authors: Halise Inci Gul; Cem Yamali; Merve Bulbuller; Petek Ballar Kirmizibayrak; Mustafa Gul; Andrea Angeli; Silvia Bua; Claudiu T. Supuran
      Pages: 290 - 297
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Halise Inci Gul, Cem Yamali, Merve Bulbuller, Petek Ballar Kirmizibayrak, Mustafa Gul, Andrea Angeli, Silvia Bua, Claudiu T. Supuran
      In this study, new dibenzensulfonamides, 7–9, having the chemical structure 4,4′-(5′-chloro-3′-methyl-5-aryl-3,4-dihydro-1′H,H-[3,4′-bipyrazole]-1′,2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7–9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7–28.1 nM and 4.5–9.3 nM, respectively.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.027
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis and evaluation of pterostilbene β-amino alcohol
           derivatives as multifunctional agents for Alzheimer's disease treatment
    • Authors: Yunxiaozhu Zheng; Xiaoming Qiang; Rui Xu; Qing Song; Chaoquan Tian; Hongyan Liu; Wei Li; Zhenghuai Tan; Yong Deng
      Pages: 298 - 306
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Yunxiaozhu Zheng, Xiaoming Qiang, Rui Xu, Qing Song, Chaoquan Tian, Hongyan Liu, Wei Li, Zhenghuai Tan, Yong Deng
      A series of pterostilbene β-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer’s disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50 = 24.04 μM), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced Aβ 1-42 aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a promising candidate for further studies directed to the development of novel drugs against AD.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.016
      Issue No: Vol. 78 (2018)
       
  • Acetylenic fatty acids from Porcelia macrocarpa (Annonaceae) against
           trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in
           plasma membrane electric potential
    • Authors: Vinicius S. Londero; Thais A. da Costa-Silva; Kaio S. Gomes; Daiane D. Ferreira; Juliana T. Mesquita; Andre G. Tempone; Maria Claudia M. Young; Gerold Jerz; João Henrique G. Lago
      Pages: 307 - 311
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Vinicius S. Londero, Thais A. da Costa-Silva, Kaio S. Gomes, Daiane D. Ferreira, Juliana T. Mesquita, Andre G. Tempone, Maria Claudia M. Young, Gerold Jerz, João Henrique G. Lago
      Porcelia macrocarpa (Warm.) R. E. Fries (Annonaceae) is an endemic plant in Brazil where its tasty pulp has been eaten fresh. The hexane extract from its flowers was subjected to chromatographic procedures to afford four acetylene derivatives identified as octadec-9-ynoic (stearolic acid – 1), (11E)-octadec-11-en-9-ynoic (santalbic acid – 2), 8-hydroxyoctadec-9,11-diynoic (3) and 8-hydroxyoctadec-17-en-9,11-diynoic (isanolic acid – 4) acids by NMR and HRESIMS. Among tested compounds against trypomastigote forms of T. cruzi, octadec-9-ynoic acid (1) displayed higher potential with IC50 = 27.6 µM and a selectivity index (SI) higher than 7. Compounds 2 and 3 showed IC50 of approximately 60 µM while compound 4 was inactive. The lethal action of the compound 1 was investigated using spectrofluorometric techniques to detect ROS content, plasma membrane permeability and plasma membrane potential by flow cytometry. Compound 1 showed no alteration in the production of ROS of treated trypomastigotes and no alteration of the plasma membrane permeability was observed as detected by the fluorescent probe SYTOX-green after 120 min of incubation. However, by using the potential-sensitive fluorescent probe DiSBAC2(3), compound 1 caused depolarization of the plasma membrane potential when compared to untreated parasites. Our results demonstrated the anti-T. cruzi effects of compounds 1–3 isolated from flowers of P. macrocarpa and indicated that the lethal effect of compound 1 in T. cruzi could be associated to the plasma membrane disturbance of the parasite.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.025
      Issue No: Vol. 78 (2018)
       
  • Tyrosine kinase inhibition effects of novel Pyrazolo[1,5-a]pyrimidines and
           Pyrido[2,3-d]pyrimidines ligand: Synthesis, biological screening and
           molecular modeling studies
    • Authors: Mardia T. El Sayed; Hoda A.R. Hussein; Nora M. Elebiary; Ghada S. Hassan; Shahenda M. Elmessery; Ahmed R. Elsheakh; Mohamed Nayel; Hatem A. Abdel-Aziz
      Pages: 312 - 323
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Mardia T. El Sayed, Hoda A.R. Hussein, Nora M. Elebiary, Ghada S. Hassan, Shahenda M. Elmessery, Ahmed R. Elsheakh, Mohamed Nayel, Hatem A. Abdel-Aziz
      Tyrosine kinases are one of the most critical mediators in the signaling path way. Late studies have proved the part of tyrosine kinases in the pathophysiology of cancer diseases. This current research paper has focused on investigating the novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines as a small molecules that can inhibit tyrosine kinase in cancer cells. NCI protocol was applied to test the antitumor activity of such compounds. Leukemia and renal cancer cell lines proved to be sensitive to some derivatives such as 6b–d, 9a and 11 with GI% values ranging from 30.4 to 41.3%. In addition, compound 11 proved to be the most active against MCF-7 with GI% 62.5. The synthesized compounds were also evaluated for their inhibitory effects against EGFR kinase enzyme. Compound 9b proved to be the most active one among the synthesized series with inhibition % value of 81.72 at 25 nM concentration and IC50 8.4 nM which is very close to the reference drug Sorafenib. In vitro cytotoxicity test was also performed using the MCF-7 breast cell line. Computer modeling using the active site of tyrosine kinase as a template and the most active tyrosine kinase inhibitors were calculated. Docking studies of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.009
      Issue No: Vol. 78 (2018)
       
  • Synthesis and molecular docking study of piperazine derivatives as potent
           inhibitor of thymidine phosphorylase
    • Authors: Imad Uddin; Muhammad Taha; Fazal Rahim; Abdul Wadood
      Pages: 324 - 331
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Imad Uddin, Muhammad Taha, Fazal Rahim, Abdul Wadood
      Thymidine phosphorylase triggers the phosphorylation of pyrimidine base to thymine and 2-deoxyribose 1-phosphate which undergoes dephosphorylation to 2-deoxyribose. It plays a role in tumor angiogenesis which is referred to the development of blood vessels during tumor growth and therefore is an attractive drug target. Keeping in view the greater importance of its inhibition, here in this study we have synthesized piperazine analogs (1–18) and evaluated for thymidine phosphorylase inhibitory activity. All analogs showed potent inhibitory potential with IC50 values ranging between 0.2 ± 0.01 and 42.20 ± 0.70 µM when compared with standard 7-Deazaxanthine (IC50 value of 38.68 ± 1.12 µM). Structure activity relationship has been also established for all newly synthesized compounds. Molecular docking studies revealed that these compounds established stronger hydrogen bonding networks with active site residues of enzyme.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.026
      Issue No: Vol. 78 (2018)
       
  • Synthesis, biological evaluation and molecular docking studies of
           aminochalcone derivatives as potential anticancer agents by targeting
           tubulin colchicine binding site
    • Authors: Guangcheng Wang; Zhiyun Peng; Jiebing Zhang; Jie Qiu; Zhenzhen Xie; Zipeng Gong
      Pages: 332 - 340
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Guangcheng Wang, Zhiyun Peng, Jiebing Zhang, Jie Qiu, Zhenzhen Xie, Zipeng Gong
      A series of aminochalcone derivatives have been synthesized, characterized by HRMS, 1H NMR and 13C NMR and evaluated for their antiproliferative activity against HepG2 and HCT116 human cancer cell lines. The most of new synthesized compounds displayed moderate to potent antiproliferative activity against test cancer cell lines. Among the derivatives, compound 4 displayed potent inhibitory activity with IC50 values ranged from 0.018 to 5.33 μM against all tested cancer cell lines including drug resistant HCT-8/T. Furthermore, this compound showed low cytotoxicity on normal human cell lines (LO2). The in vitro tubulin polymerization assay showed that compound 4 inhibited tubulin assembly in a concentration-dependent manner with IC50 value of 7.1 μM, when compared to standard colchicine (IC50 = 9.0 μM). Further biological evaluations revealed that compound 4 was able to arrest the cell cycle in G2/M phase. Molecular docking study demonstrated the interaction of compound 4 at the colchicine binding site of tubulin. All the results indicated that compound 4 is a promising inhibitor of tubulin polymerization for the treatment of cancer.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.028
      Issue No: Vol. 78 (2018)
       
  • New advances in synthesis and clinical aspects of
           pyrazolo[3,4-d]pyrimidine scaffolds
    • Authors: Khaled R.A. Abdellatif; Rania B. Bakr
      Pages: 341 - 357
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Khaled R.A. Abdellatif, Rania B. Bakr
      Pyrazolo[3,4-d]pyrimidine ring system constitute an important class of heterocyclic compounds which can serve as a promising scaffold exhibiting many pharmacological activities. This ring system received much attention as it is a purine isostere by replacing imidazole ring in purine with pyrazole moiety in pyrazolo[3,4-d]pyrimidine. Here we concentrate on new advances in the synthesis of this important ring and other clinical aspects in an attempt to sheld the light to assist in discovery of new pyrazolo[3,4-d]pyrimidine derivatives.

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.032
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis and evaluation of some pyrazolo[3,4-d]pyrimidines as
           anti-inflammatory agents
    • Authors: Gina N. Tageldin; Salwa M. Fahmy; Hayam M. Ashour; Mounir A. Khalil; Rasha A. Nassra; Ibrahim M. Labouta
      Pages: 358 - 371
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Rasha A. Nassra, Ibrahim M. Labouta
      New pyrazolo[3,4-d]pyrimidines substituted with various functionalities or attached to a substituted pyrazole ring through different linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity using in vitro COX-1/COX-2 inhibition assay and in vivo formalin induced paw edema and cotton pellet-induced granuloma assays. Results revealed that compounds 17b and 18 possessed COX-1/COX-2 selectivity indices higher than diclofenac sodium and celecoxib. However, compounds 16a,b exhibited selectivity indices higher than diclofenac sodium and nearly equivalent to celecoxib, whereas, 9b displayed selectivity index comparable to diclofenac sodium. In vivo anti-inflammatory data showed that compounds 9b, 16a, 18 displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, the pyrazolyl derivatives 9b, 16b and 17b displayed anti-inflammatory activity about 2–2.5-fold that of diclofenac sodium and nearly 8–10.5-fold that of celecoxib in the cotton pellet-induced granuloma assay. The ulcerogenic effect of the active compounds was also investigated and results revealed that compounds 16a, 17a,b and 18 showed good gastrointestinal safety profile. Based on this, compounds 16a and 18 were considered as safe and effective leads in managing acute inflammation, while, 17b was prominent in controlling chronic inflammation.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.030
      Issue No: Vol. 78 (2018)
       
  • Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive
           prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells
           
    • Authors: V. Herceg; S. Adriouach; K. Janikowska; E. Allémann; N. Lange; A. Babič
      Pages: 372 - 380
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): V. Herceg, S. Adriouach, K. Janikowska, E. Allémann, N. Lange, A. Babič
      Treatment of cancer cells by clinically approved hexyl ester of 5-aminolevulinic acid (ALA-Hex) induces accumulation of fluorescent porphyrins in tumors. This allows fluorescence photodiagnosis (PD) of bladder cancer by blue light illumination. However, PD of other cancers is hampered by acute toxicity of the compound limiting its use to local applications. We have designed and synthesized a new prodrug of ALA-Hex that tackles the stability-activity paradox of amino-modified 5-ALA prodrugs. The glucuronide prodrug Glu-ALA-Hex demonstrates excellent stability under physiological conditions and activation in the presence of the target enzyme. β-glucuronidase-triggered release of 5-ALA is programmed to yield fluorescence in tumor environment with elevated β-glucuronidase activity, a characteristic of many solid tumors. Glu-ALA-Hex produces similar levels of fluorescence as ALA-Hex in breast cancer MCF7 cells in vitro but with much lower non-specific cell toxicity.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.020
      Issue No: Vol. 78 (2018)
       
  • Glycosyl glycerides from the aerial parts of Malva verticillata and their
           chemopreventive effects
    • Authors: Jung-Hwan Ko; Se Min Cho; Sun-Woo Joo; Hyoung-Geun Kim; Yeong-Geun Lee; Se Chan Kang; Nam-In Baek
      Pages: 381 - 392
      Abstract: Publication date: August 2018
      Source:Bioorganic Chemistry, Volume 78
      Author(s): Jung-Hwan Ko, Se Min Cho, Sun-Woo Joo, Hyoung-Geun Kim, Yeong-Geun Lee, Se Chan Kang, Nam-In Baek
      A new glycosyl glyceride (5) along with twelve known ones (1–4 and 6–13) including two sulfoquinovosyl glycerides (1 and 2) were isolated from the aerial parts of Malva verticillata. Based on several spectroscopic methods, compound 5 was identified to be (2S)-1-O-β-d-galactopyranosyl-3-O-isostearoyl glyceride, and named malvaglycolipid A. Compounds 1 and 2 contained a unique sugar, (6-deoxy-6-sulfo)-α-d-glucopyranose, which very rarely occurs in natural sources. This is the first report for the isolation of compounds 1 and 2 from natural sources and the structure determination using NMR experiment. It was also of note that no glycosyl glyceride has previously been isolated from the family of Malvaeae. Most glycosyl glycerides showed cytotoxicity to HepG2, AGS, HCT-15, and A549 human cancer cells. Especially, compounds 1, 2, and 11 exhibited significant cytotoxicity to AGS cells, with IC50 values of 33.7 ± 0.64 μM, 11.1 ± 0.07 μM, and 10.6 ± 0.10 μM, respectively. The n-BuOH fraction and compounds 1, 2, and 11 increased the number of apoptotic cells in the Tali assay and had a significant effect on the levels of proteins related to apoptosis including PARP, caspase-3, Bcl-2, Bax, and β-actin.
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      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.013
      Issue No: Vol. 78 (2018)
       
  • Synthesis, molecular modelling studies and ADME prediction of
           benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their
           anti-diabetic activity through in vivo model
    • Authors: Rubina Bhutani; Dharam Pal Pathak; Garima Kapoor; Asif Husain; Ravi Kant; Md. Azhar Iqbal
      Pages: 6 - 15
      Abstract: Publication date: April 2018
      Source:Bioorganic Chemistry, Volume 77
      Author(s): Rubina Bhutani, Dharam Pal Pathak, Garima Kapoor, Asif Husain, Ravi Kant, Md. Azhar Iqbal
      A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ± 4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ± 1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski’s rule of five.
      Graphical abstract image

      PubDate: 2018-01-10T14:25:48Z
      DOI: 10.1016/j.bioorg.2017.12.037
      Issue No: Vol. 77 (2018)
       
  • Synthesis and biological evaluation of naphthalimide-polyamine conjugates
           modified by alkylation as anticancer agents through p53 pathway
    • Authors: Fujun Dai; Haoying He; Xiaojuan Xu; Shuai Chen; Chaojie Wang; Chenyang Feng; Zhiyong Tian; Huanyang Dong; Songqiang Xie
      Pages: 16 - 24
      Abstract: Publication date: April 2018
      Source:Bioorganic Chemistry, Volume 77
      Author(s): Fujun Dai, Haoying He, Xiaojuan Xu, Shuai Chen, Chaojie Wang, Chenyang Feng, Zhiyong Tian, Huanyang Dong, Songqiang Xie
      In this study, a series of novel naphthalimide-polyamine conjugates modified by alkylation at the terminal of the polyamine chain were synthesized. These novel conjugates were evaluated for their anti-cancer activities. The results revealed that the length of the polyamine chain and the terminal alkyl group had influences on anticancer activities. Compound 3g was chosen to further study the anti-cancer mechanism and evaluate the anti-tumor efficacy in vivo. It induced intrinsic apoptosis and suppressed migration of hepatoma cells. The preliminary studies of compound 3g in vivo showed that it might be a promising candidate for cancer therapy.
      Graphical abstract image

      PubDate: 2018-01-10T14:25:48Z
      DOI: 10.1016/j.bioorg.2017.12.036
      Issue No: Vol. 77 (2018)
       
  • Novel sulfonamide incorporating piperazine, aminoalcohol and
           1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX
           inhibitory action
    • Authors: Eva Havránková; Jozef Csöllei; Daniela Vullo; Vladimír Garaj; Pavel Pazdera; Claudiu T. Supuran
      Pages: 25 - 37
      Abstract: Publication date: April 2018
      Source:Bioorganic Chemistry, Volume 77
      Author(s): Eva Havránková, Jozef Csöllei, Daniela Vullo, Vladimír Garaj, Pavel Pazdera, Claudiu T. Supuran
      A new series of s-triazine derivatives incorporating sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide and piperazine or aminoalcohol structural motifs is reported. Molecular docking was exploited to select compounds from virtual combinatorial library for synthesis and subsequent biological evaluation. The compounds were prepared by using step by step nucleophilic substitution of chlorine atoms from cyanuric chloride (2,4,6-trichloro-1,3,5-triazine). The compounds were tested as inhibitors of physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms. Specifically, against the cytosolic hCA I, II and tumor-associated hCA IX. These compounds show appreciable inhibition. hCA I was inhibited with K Is in the range of 8.5–2679.1 nM, hCA II with K Is in the range of 4.8–380.5 nM and hCA IX with K Is in the range of 0.4–307.7 nM. As other similar derivatives, some of the compounds showed good or excellent selectivity ratios for inhibiting hCA IX over hCA II, of 3.5–18.5. 4-[({4-Chloro-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)methyl] benzene sulfonamide demonstrated subnanomolar affinity for hCA IX (0.4 nM) and selectivity (18.50) over the cytosolic isoforms. This series of compounds may be of interest for the development of new, unconventional anticancer drugs targeting hypoxia-induced CA isoforms such as CA IX.
      Graphical abstract image

      PubDate: 2018-01-10T14:25:48Z
      DOI: 10.1016/j.bioorg.2017.12.034
      Issue No: Vol. 77 (2018)
       
  • Synthesis, biological evaluation and molecular modeling of novel
           thienopyrimidinone and triazolothienopyrimidinone derivatives as dual
           anti-inflammatory antimicrobial agents
    • Authors: Adnan A. Bekhit; Ahmed M. Farghaly; Ragab M. Shafik; Mona M.A. Elsemary; Alaa El-Din A. Bekhit; Aida A. Guemei; Mai S. El-Shoukrofy; Tamer M. Ibrahim
      Pages: 38 - 46
      Abstract: Publication date: April 2018
      Source:Bioorganic Chemistry, Volume 77
      Author(s): Adnan A. Bekhit, Ahmed M. Farghaly, Ragab M. Shafik, Mona M.A. Elsemary, Alaa El-Din A. Bekhit, Aida A. Guemei, Mai S. El-Shoukrofy, Tamer M. Ibrahim
      New thienopyrimidinone and triazolothienopyrimidinone derivatives have been synthesized. These compounds were subjected to anti-inflammatory and antimicrobial activity screening aiming to identify new candidates that have dual anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed minimal ulcerogenic effect and high selectivity towards human recombinant COX-2 over COX-1 enzyme. Their docking outcome correlated with their biological activity and assured the high selectivity binding towards COX-2. In addition, they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The antimicrobial screening showed that compound 10a displayed distinctive inhibitory effect on the growth of Escherichia coli comparable to that of ampicillin. Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of ampicillin against E. coli. Thus, compounds 5, 7 and 10a represent promising dual acting anti-inflammatory and antimicrobial agents. This work provides rewarding template enriching the chemical space for dual anti-inflammatory anti-microbial activities.
      Graphical abstract image

      PubDate: 2018-01-10T14:25:48Z
      DOI: 10.1016/j.bioorg.2017.12.028
      Issue No: Vol. 77 (2018)
       
  • Design, synthesis and biological evaluation of pyrimidine-based
           derivatives as VEGFR-2 tyrosine kinase inhibitors
    • Authors: Wuji Sun; Shengquan Hu; Shubiao Fang; Hong Yan
      Abstract: Publication date: Available online 13 April 2018
      Source:Bioorganic Chemistry
      Author(s): Wuji Sun, Shengquan Hu, Shubiao Fang, Hong Yan
      Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has already become an attractive approach for cancer therapy. In this study, a novel pyrimidine-based derivative 7j was designed as lead compound, and three series of potent VEGFR-2 inhibitors were synthesized and biologically evaluated against A549 and HepG2 cell lines. Compounds 7d, 9s and 13n exhibited superior inhibitory activities against A549 cell with IC50 ranged from 9.19 to 13.17 μM and HepG2 cell with IC50 ranged from 11.94 to 18.21 μM compared to those of Pazopanib (IC50=21.18 and 36.66 μM). In addition, molecular docking study was performed to investigate the binding capacity and binding mode between target compounds and VEGFR-2.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.04.005
       
  • Synthesis and molecular docking study of piperazine derivatives as potent
           urease inhibitors
    • Authors: Muhammad Taha; Abdul Wadood
      Abstract: Publication date: Available online 13 April 2018
      Source:Bioorganic Chemistry
      Author(s): Muhammad Taha, Abdul Wadood
      Urease is known to be one of the major causes of diseases induced by Helicobacter pylori, thus allow them to survive at low pH inside the stomach and thereby, play an important role in the pathogenesis of gastric and peptic ulcer, apart from cancer as well. Keeping in view the great importance of urease inhibitors, here in this study we have synthesized piperazine derivatives (1-15) and evaluated for their urease inhibitory activity. All analogs showed excellent inhibitory potential with IC50 values ranging between 1.1 ± 0.01to 33.40 ± 1.50 µM when compared with the standard inhibitor thiourea (IC50 = 21.30 ± 1.10 µM). Structure activity relationship has been established for all compounds which are mainly based upon the substitution on phenyl ring. Molecular docking study was performed in order to understand the binding interaction of the compounds in the active site of enzyme.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.04.007
       
  • Differential metabolism of diastereoisomeric diterpenes by Preussia
           minima, found as endophytic fungus in Cupressus lusitanica
    • Authors: Zia ud Din; L.S. de Medeiros; L.M. Abreu; Ludwig H. Pfenning; D.B. Lopes Jymeni; E. Rodrigues-Filho
      Abstract: Publication date: Available online 12 April 2018
      Source:Bioorganic Chemistry
      Author(s): Zia ud Din, L.S. de Medeiros, L.M. Abreu, Ludwig H. Pfenning, D.B. Lopes Jymeni, E. Rodrigues-Filho
      The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface sterilized stems of C. lusitanica. The ent-pimaradienoic acid was transformed into the known 7β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid, and into the novel diterpenes 7-oxo-8 β-hydroxy-ent-pimara-8(14)-15-dien-19-oic and 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acids. Isopimara-8(14)-15-dien-18-oic acid was converted into novel diterpenes 11α-hydroxyisopimara-8(14)-15-dien-18-oic acid, 7β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, and 1β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, along with the known 7β-hydroxyisopimara-8(14)-15-dien-18-oic acid. All compounds were isolated and fully characterized by 1D and 2D NMR, especially 13C NMR. The diterpene bioproduct 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid is an isomer of sphaeropsidin C, a phytotoxin that affects cypress trees produced by Shaeropsis sapinea, one of the main phytopathogen of Cupressus. The differential metabolism of the diterpene isomers used as substrates for biotransformation was interpreted with the help of computational molecular docking calculations, considering as target enzymes those of cytochrome P450 group.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.04.003
       
  • Design, synthesis, biological evaluation, structure-activity relationship
           study, and mode of action of 2-phenol-4,6-dichlorophenyl-pyridines
    • Authors: Aarajana Shrestha; Seojeong Park; Somin Shin; Tara Man Kadayat; Ganesh Bist; Pramila Katila; Youngjoo Kwon; Eung-Seok Lee
      Abstract: Publication date: Available online 3 April 2018
      Source:Bioorganic Chemistry
      Author(s): Aarajana Shrestha, Seojeong Park, Somin Shin, Tara Man Kadayat, Ganesh Bist, Pramila Katila, Youngjoo Kwon, Eung-Seok Lee
      Human DNA topoisomerases (Topos) are essential nuclear enzyme whose level of expression is potential indicator for prediction of responsive result of chemotherapy. Topos has become a key cellular target for most of the anticancer agents that regulates topological problems of DNA during cellular metabolic processes such as replication, transcription, and recombination. Inspired by previous studies of 2,4,6-trisubstituted pyridines to find out safer and effective topoisomerase targeted anticancer agent, twenty-seven 2-phenol-4,6-dichlorophenyl-pyridines were designed, synthesized, and tested for their topo I and IIα inhibitory and anti-proliferative activity. Most of the dichlorinated meta- and para-phenolic series compounds (1-18) exhibited potent and selective topo IIα inhibition along with significant anti-proliferative activity in the HCT-15 and T47D cell lines compared to the positive control, etoposide. Interestingly, dichlorinated ortho-phenolic series compounds (19-27) exhibited potent and dual topo inhibition but very weak anti-proliferative activity in the tested cancer cell lines. Structure-activity relationship with previously synthesized compounds revealed the importance of chlorine moiety to improve the potency of topo inhibitory activity. Further mechanistic study confirmed that compounds 2 and 12 acted as non-intercalative specific topo IIα catalytic inhibitor with less DNA damage, and induced G1 arrest and apoptosis in HCT-15 and T47D cell lines, respectively.
      Graphical abstract image

      PubDate: 2018-04-16T13:17:24Z
      DOI: 10.1016/j.bioorg.2018.03.033
       
  • Issue TOC
    • Abstract: Publication date: April 2018
      Source:Bioorganic Chemistry, Volume 77


      PubDate: 2018-04-16T13:17:24Z
       
 
 
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