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CHEMISTRY (598 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 8)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26)
ACS Catalysis     Full-text available via subscription   (Followers: 32)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 17)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 23)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 226)
ACS Photonics     Full-text available via subscription   (Followers: 11)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 7)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 50)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 53)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 14)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 19)
Advances in Nanoparticles     Open Access   (Followers: 14)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 41)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 26)
American Journal of Plant Physiology     Open Access   (Followers: 13)
American Mineralogist     Hybrid Journal   (Followers: 13)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 159)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 210)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 1)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 14)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 3)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 282)
Biochemistry Insights     Open Access   (Followers: 5)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 1)
Biomacromolecules     Full-text available via subscription   (Followers: 19)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 4)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 108)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 93)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 3)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 67)
Catalysis for Sustainable Energy     Open Access   (Followers: 6)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 6)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 7)
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: 12)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 70)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 23)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 19)
Chemical Reviews     Full-text available via subscription   (Followers: 173)
Chemical Science     Open Access   (Followers: 21)
Chemical Technology     Open Access   (Followers: 16)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 8)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 55)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 25)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 147)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 18)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 45)
Chemistry of Materials     Full-text available via subscription   (Followers: 250)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access  
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 2)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 9)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Chromatography Research International     Open Access   (Followers: 7)
Clay Minerals     Full-text available via subscription   (Followers: 9)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 8)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 3)
Combustion Science and Technology     Hybrid Journal   (Followers: 18)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 2)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 2)
Copernican Letters     Open Access  
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 3)
CrystEngComm     Full-text available via subscription   (Followers: 11)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 57)
Dalton Transactions     Full-text available via subscription   (Followers: 19)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 4)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 4)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Elements     Full-text available via subscription   (Followers: 2)
Environmental Chemistry     Hybrid Journal   (Followers: 9)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)

        1 2 3 | Last

Journal Cover Bioorganic Chemistry
  [SJR: 0.926]   [H-I: 43]   [10 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0045-2068 - ISSN (Online) 1090-2120
   Published by Elsevier Homepage  [3042 journals]
  • Enantioselectivity of Haloalkane Dehalogenase LinB on the Degradation of
           1,2-Dichloropropane: A QM/MM Study
    • Authors: Xiaowen Tang; Ruiming Zhang; Yanwei Li; Qingzhu Zhang; Wenxing Wang
      Pages: 16 - 23
      Abstract: Publication date: Available online 12 May 2017
      Source:Bioorganic Chemistry
      Author(s): Xiaowen Tang, Ruiming Zhang, Yanwei Li, Qingzhu Zhang, Wenxing Wang
      The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8 kcal/mol for the (R)-isomer and 24.0 kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.
      Graphical abstract image

      PubDate: 2017-05-16T11:27:51Z
      DOI: 10.1016/j.bioorg.2017.04.015
      Issue No: Vol. 73 (2017)
  • DFT/B3LYP calculations, in vitro cytotoxicity and antioxidant activities
           of steroidal pyrimidines and their interaction with HSA using molecular
           docking and multispectroscopic techniques
    • Authors: Abad Ali; Mohd Asif; Parvez Alam; Mohammad Jane Alam; Mohd. Asif Sherwani; Rizwan Hasan Khan; Shabbir Ahmad; Shamsuzzaman
      Pages: 83 - 99
      Abstract: Publication date: August 2017
      Source:Bioorganic Chemistry, Volume 73
      Author(s): Abad Ali, Mohd Asif, Parvez Alam, Mohammad Jane Alam, Mohd. Asif Sherwani, Rizwan Hasan Khan, Shabbir Ahmad, Shamsuzzaman
      As a part of our continuing program on the synthesis of steroidal heterocycles, it has been prepared a series of novel steroidal pyrimidine derivatives 4–6 via TMSCl, steroidal ketones (1c–3c), urea and benzaldehyde. The systems presented here, are novel scaffolds and have not been described before at 6th position of steroidal-6-one (1c–3c). Structural assignment of newly synthesized compounds was performed by DFT/B3LYP calculations as well as spectral and analytical data. The interactions of compounds (4–6) with HSA were studied by fluorescence spectroscopy, DLS, CD and molecular docking, under imitated physiological conditions. The antitumor activity has been tested in vitro against three cancer cell lines MDA-MB231 (breast carcinoma), HeLa (human cervical carcinoma), HepG2 (hepatic carcinoma) and one non-cancer normal cell lines, PBMCs (peripheral blood mononuclear cell) by MTT assay. In addition, in vitro antioxidant activity and apoptosis assay of the synthesized compounds (4–6) have also been investigated.
      Graphical abstract image

      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.001
      Issue No: Vol. 73 (2017)
  • 5-Bromo-2-Aryl benzimidazole Derivatives as Non-Cytotoxic Potential Dual
           Inhibitors of α-Glucosidase and Urease Enzymes
    • Authors: Tanzila Arshad; Khalid Mohammed Khan; Najma Rasool; Uzma Salar; Shafqat Hussain; Humna Asghar; Mohammed Ashraf; Abdul Wadood; Muhammad Riaz; Shahnaz Perveen; Muhammad Taha; Nor Hadiani Ismail
      Pages: 21 - 31
      Abstract: Publication date: Available online 20 March 2017
      Source:Bioorganic Chemistry
      Author(s): Tanzila Arshad, Khalid Mohammed Khan, Najma Rasool, Uzma Salar, Shafqat Hussain, Humna Asghar, Mohammed Ashraf, Abdul Wadood, Muhammad Riaz, Shahnaz Perveen, Muhammad Taha, Nor Hadiani Ismail
      On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50 = 8.15 ± 0.03-354.67 ± 0.19 μM) as compared to standard thiourea (IC50 = 21.25 ± 0.15 μM). It is worth mentioning that derivatives 7 (IC50 = 12.07 ± 0.05 μM), 8 (IC50 = 10.57 ± 0.12 μM), 11 (IC50 = 13.76 ± 0.02 μM), 14 (IC50 = 15.70 ± 0.12 μM) and 22 (IC50 = 8.15 ± 0.03 μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e. 2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
      Graphical abstract image

      PubDate: 2017-03-26T17:16:55Z
      DOI: 10.1016/j.bioorg.2017.03.007
      Issue No: Vol. 72 (2017)
  • Protective Effects of Hepatocyte-Specific Glycyrrhetic Derivatives against
           Carbon Tetrachloride-Induced Liver Damage in Mice
    • Authors: Yifei Yang; Lingyun Yang; Yaodan Han; Zhenwei Wu; Pan Chen; Huibin Zhang; Jinpei Zhou
      Pages: 42 - 50
      Abstract: Publication date: Available online 20 March 2017
      Source:Bioorganic Chemistry
      Author(s): Yifei Yang, Lingyun Yang, Yaodan Han, Zhenwei Wu, Pan chen, Huibin Zhang, Jinpei Zhou
      Glycyrrhetic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the roots of the Chinese herb Glycyrrhiza glabra, was reported to be accumulated in hepatocytes due to the extensive distribution of GA receptors in liver. A series of hepatocyte-specific derivatives on the basis of anetholtrithione and glycyrrhizic were designed and synthesized. The potential beneficial effect was evaluated in carbon tetrachloride (CCl4)-induced liver injury model. In addition, the hepatoprotective activity of these derivatives was assessed by measuring levels of serum marker enzymes, including serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and the ratio of GSH to GSSG. Gratifyingly, compounds 5a-c (100 mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT. A comparative histopathological study of liver exhibited almost a normal liver lobular architecture and cell structure of the livers, as compared to CCl4-treated group. These findings were confirmed with the histopathological observations, where hepatocyte-specific glycyrrhetic acid derivatives 5a-c were capable of reversing the toxic effects of CCl4 on hepatocytes.
      Graphical abstract image

      PubDate: 2017-03-26T17:16:55Z
      DOI: 10.1016/j.bioorg.2017.03.009
      Issue No: Vol. 72 (2017)
  • Aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new
           potential antitrypanosomal agents
    • Authors: Angel H. Romero; Jonathan Rodríguez; Yael García-Marchan; Jacques Leañez; Xenón Serrano-Martín; Simón E. López
      Pages: 51 - 56
      Abstract: Publication date: Available online 21 March 2017
      Source:Bioorganic Chemistry
      Author(s): Angel H. Romero, Jonathan Rodríguez, Yael García, Jacques Leañez, Xenón Serrano-Martín, Simón E. López
      A series of twenty phthalazinyl-hydrazones were synthesized and tested as potential anti-Trypanosoma cruzi agents. The phthalazines containing 5-nitroheteroaryl moiety 3l and 3m displayed an excellent in vitro antitrypanosomal profile, exhibiting low micromolar EC50 values against proliferative epimastigote of T. cruzi and minimal toxicity toward Vero cells. These derivatives were more potent than the reference drug benznidazole against the epimastigote stage of the parasite. Structure-property analysis indicates that the highly conjugated 5-nitroheteroaryl moiety connected to the phthalazin scaffold play an important role in the antichagasic activity of these phthalazines. The decrease on the mitochondrial dehydrogenase activity and significant ROS production found for the parasites treated with 3l and 3m suggest that both nitro-derivatives can act through an oxidative stress mechanism.
      Graphical abstract image

      PubDate: 2017-03-26T17:16:55Z
      DOI: 10.1016/j.bioorg.2017.03.008
      Issue No: Vol. 72 (2017)
  • A natural product from Cannabis sativa subsp. sativa inhibits
           homeodomain-interacting protein kinase 2 (HIPK2), attenuating MPP+-induced
           apoptosis in human neuroblastoma SH-SY5Y cells
    • Authors: Guan Wang; Lingjuan Zhu; Yuqian Zhao; Suyu Gao; Dejuan Sun; Jingquan Yuan; Yuxin Huang; Xue Zhang; Xinsheng Yao
      Pages: 64 - 73
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Guan Wang, Lingjuan Zhu, Yuqian Zhao, Suyu Gao, Dejuan Sun, Jingquan Yuan, Yuxin Huang, Xue Zhang, Xinsheng Yao
      Homeodomain-interacting protein kinase 2 (HIPK2) is a conserved serine/threonine kinase, which regulate transcription, cell differentiation, proliferation and apoptosis. Previous evidences indicated that HIPK2 could be involved in the pathogenesis of neurodegenerative diseases, suggesting as a novel target for Parkinson’s disease (PD) therapeutic development. Herein, gene microarray analysis was performed to verify the key regulatory function of HIPK2 in PD. (Z)-methyl p-hydroxycinnamate (ZMHC, 7) with other eighteen compounds were isolated from Cannabis sativa subsp. sativa, growing in Bama Yao Autonomous County, one of the five largest longevity regions of the world. Intriguingly, ZMHC was identified to bind HIPK2 with high affinity through molecular modeling and molecular dynamics (MD) simulations. Moreover, cell morphology, flow cytometry and western blot assay suggested that ZMHC inhibited HIPK2, which attenuated MPP+-induced apoptosis in SH-SY5Y cells. In conclusion, these findings discovered a natural product that inhibited HIPK2, and highlighted that ZMHC could be a potential precursor agent for future PD therapy.
      Graphical abstract image

      PubDate: 2017-04-03T15:08:13Z
      DOI: 10.1016/j.bioorg.2017.03.011
      Issue No: Vol. 72 (2017)
  • Synthesis and study of anti-HIV-1 RT activity of
    • Authors: Subhash Chander; Cheng-Run Tang; Helmi Mohammed Al-Maqtari; Joazaizulfazli Jamalis; Ashok Penta; Taibi Ben Hadda; Hasnah Mohd Sirat; Yong-Tang Zheng; Murugesan Sankaranarayanan
      Pages: 74 - 79
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Subhash Chander, Cheng-Run Tang, Helmi Mohammed Al-Maqtari, Joazaizulfazli Jamalis, Ashok Penta, Taibi Ben Hadda, Hasnah Mohd Sirat, Yong-Tang Zheng, Murugesan Sankaranarayanan
      In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50 ≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.
      Graphical abstract image

      PubDate: 2017-04-03T15:08:13Z
      DOI: 10.1016/j.bioorg.2017.03.013
      Issue No: Vol. 72 (2017)
  • Synthesis and preliminary biological assay of uridine glycoconjugate
           derivatives containing amide and/or 1,2,3-triazole linkers
    • Authors: Gabriela Pastuch-Gawolek; Mateusz Plesniak; Roman Komor; Anna Byczek-Wyrostek; Karol Erfurt; Wieslaw Szeja
      Pages: 80 - 88
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Gabriela Pastuch-Gawolek, Mateusz Plesniak, Roman Komor, Anna Byczek-Wyrostek, Karol Erfurt, Wieslaw Szeja
      A series of UDP-sugar analogues was synthesized and their preliminary biological activity was evaluated. Glycoconjugates of uridine 1 and 2 were synthesized by condensation of uridine-5′-carboxylic acid and 1-amino sugars derivatives of d-glucose and d-galactose, glycoconjugates 3 and 4 were synthesized by azide-alkyne 1,3-dipolar cycloaddition (CuAAC) of 1-azido sugars and propargylamide derivatives of uridine while glycoconjugates 5 and 6 were synthesized by CuAAC of propargyl β-O-glycosides and 5′-azido uridine. Evaluation of inhibitory activity of compounds 1–6 against commercially available β-1,4-galactosyltransferase I (β4GalT) show that compound 5 inhibited the enzyme in µmolar range. Additionally, the antitumor activity of the obtained glycoconjugates 1–6 were tested using MTT assay.
      Graphical abstract image

      PubDate: 2017-04-03T15:08:13Z
      DOI: 10.1016/j.bioorg.2017.03.015
      Issue No: Vol. 72 (2017)
  • Cytotoxic effects of a novel maleimide derivative on epithelial and tumor
    • Authors: Bakat Ali; Léonard D. Kanda Kupa; Cíntia S. Heluany; Carine C. Drewes; Stanley N.S. Vasconcelos; Sandra H.P. Farsky; Hélio A. Stefani
      Pages: 199 - 207
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Bakat Ali, Léonard D. Kanda Kupa, Cíntia S. Heluany, Carine C. Drewes, Stanley N.S. Vasconcelos, Sandra H.P. Farsky, Hélio A. Stefani
      Novel N-triazolyl maleimide derivatives were synthesized by azide–alkyne Huisgen cycloaddition (1,3-dipolar cycloaddition) and tested for cytotoxicity against a cell line derived from human melanomas SK-Mel-28 and SK-Mel-103, and human umbilical vein endothelial cell lines (HUVEC). The 4l was chose to be biologically tested due to incorporation of benzyl triazolic to the nitrogen of maleimide has not been tested before, and due the satisfactory yield. The analysis of cell metabolism, using the MTT method, showed that the compound 4l impaired cell metabolism in HUVEC only in high concentration (100µM). A lower concentration of compound 4l, whether in association or not with paclitaxel, was required to cause toxicity in both SK-Mel-28 and SK-Mel-103 cells in comparison with HUVEC cells. Moreover, the ability of 4l to cause cell death was evaluated by flow cytometry, and the data obtained highlighted the apoptotic action of 4l and paclitaxel co-treatment on Sk-Mel-28 cells only, which corroborated the greater efficacy of maleimide compounds against cancer cells. Together, our data provide promising data on the selectivity of maleimide compounds to cancer cells, and suggest that novel maleimide-substituted compounds may be synthesized and tested on different cancer cell lines, as primary or co-adjuvant agents of cancer cell toxicity.
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      PubDate: 2017-04-30T18:34:37Z
      DOI: 10.1016/j.bioorg.2017.04.013
      Issue No: Vol. 72 (2017)
  • Novel multi-targeted agents for Alzheimer's disease: Synthesis, biological
           evaluation, and molecular modeling of novel
    • Authors: Keriman Ozadali-Sari; Tuba Tüylü Küçükkılınç; Beyza Ayazgok; Ayla Balkan; Oya Unsal-Tan
      Pages: 208 - 214
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Keriman Ozadali-Sari, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Ayla Balkan, Oya Unsal-Tan
      The present study describes the synthesis, pharmacological evaluation (BChE/AChE inhibition, Aβ antiaggregation, and neuroprotective effects), and molecular modeling studies of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazole derivatives. The alkyl-substituted derivatives exhibited selective inhibition on BChE with varying efficiency. Compounds 3b and 3d were found to be the most potent inhibitors of BChE with IC50 values of 5.18 and 5.22μM, respectively. The kinetic studies revealed that 3b is a partial non-competitive BChE inhibitor. Molecular modeling studies also showed that the alkyl-substituted derivatives were able to reach the catalytic anionic site of the BChE. The compounds with an inhibitory effect on BChE were subsequently screened for their Aβ antiaggregating and neuroprotective activities. Compounds 3a and 3b exerted a potential neuroprotective effect against H2O2 and Aβ-induced cytotoxicity in SH-SY5Y cells. Collectively, 3b was found as the most promising compound for the development of multi-target directed ligands against Alzheimer’s disease.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.04.018
      Issue No: Vol. 72 (2017)
  • Discovery of 3,3-di(indolyl)indolin-2-one as a novel scaffold for
           α-glucosidase inhibitors: In silico studies and SAR predictions
    • Authors: Guangcheng Wang; Jing Wang; Zhenzhen Xie; Ming Chen; Luyao Li; Yaping Peng; Shan Chen; Wenbiao Li; Bin Deng
      Pages: 228 - 233
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Guangcheng Wang, Jing Wang, Zhenzhen Xie, Ming Chen, Luyao Li, Yaping Peng, Shan Chen, Wenbiao Li, Bin Deng
      3,3-Di(indolyl)indolin-2-ones 4a-4n were synthesized and evaluated for their in vitro α-glucosidase inhibitory activity. These newly synthesized compounds showed moderate to potent α-glucosidase inhibitory activity with IC50 range from 5.98±0.11 to 145.95±0.46μM, when compared to the standard drug acarbose. Among this series of 3,3-di(indolyl)indolin-2-ones, compound 4j (5.98±0.11μM) having a 2-fluorobenzyl group on the indole ring was found to be the most active compound. Molecular docking studies showed that compound 4j have high binding affinities with the active site of α-glucosidase enzyme through hydrogen bonds, arene-cation, π-π stacking and hydrophobic interactions. This study showed these 3,3-di(indolyl)indolin-2-ones as a new class of α-glucosidase inhibitors.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.006
      Issue No: Vol. 72 (2017)
  • Rational design, synthesis, pharmacophore modeling, and docking studies
           for identification of novel potent DNA-PK inhibitors
    • Authors: Saleh Ihmaid; Hany E.A. Ahmed; Adeeb Al-Sheikh Ali; Yousery E. Sherif; Hamadeh M. Tarazi; Sayed M. Riyadh; Mohamed F. Zayed; Hamada S. Abulkhair; Heba S. Rateb
      Pages: 234 - 247
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Saleh Ihmaid, Hany E.A. Ahmed, Adeeb Al-Sheikh Ali, Yousery E. Sherif, Hamadeh M. Tarazi, Sayed M. Riyadh, Mohamed F. Zayed, Hamada S. Abulkhair, Heba S. Rateb
      Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7-yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinski's rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25 to 5µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.04.014
      Issue No: Vol. 72 (2017)
  • DNA fluorescent labeling with naphtho[1,2,3-cd]indol-6(2H)-one for
           investigation of protein-DNA interactions
    • Authors: Svetlana V. Vasilyeva; Nikita A. Kuznetsov; Anastasya S. Kuznetsova; Juliya G. Khalyavina; Darya A. Tropina; Tatyana I. Lavrikova; Olga I. Kargina; Leonid M. Gornostaev
      Pages: 268 - 272
      Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72
      Author(s): Svetlana V. Vasilyeva, Nikita A. Kuznetsov, Anastasya S. Kuznetsova, Juliya G. Khalyavina, Darya A. Tropina, Tatyana I. Lavrikova, Olga I. Kargina, Leonid M. Gornostaev
      Fluorescently labeled DNA to study protein-DNA interactions was synthesized using the Cu(I)-catalysed cycloaddition (CuAAC) reaction. For this purpose, a new azido-containing fluorophore based on the naphtho[1,2,3-cd]indol-6(2H)-one derivative was obtained. The fluorescent properties of naphtho[1,2,3-cd]indol-6(2H)-one derivatives and labeled DNA were studied. The new fluorescent DNA conjugate was shown to be a useful tool to study complex mechanisms of protein-DNA interactions.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.002
      Issue No: Vol. 72 (2017)
  • Target Identification, Lead Optimization and Antitumor Evaluation of Some
           New 1,2,4-Triazines as c-Met Kinase Inhibitors
    • Authors: Marwa H. El-Wakil; Hayam M. Ashour; Manal N. Saudi; Ahmed M. Hassan; Ibrahim M. Labouta
      Abstract: Publication date: Available online 27 June 2017
      Source:Bioorganic Chemistry
      Author(s): Marwa H. El-Wakil, Hayam M. Ashour, Manal N. Saudi, Ahmed M. Hassan, Ibrahim M. Labouta
      In silico target fishing approach using PharmMapper server identified c-Met kinase as the selective target for our previously synthesized compound NCI 748494/1. This approach was validated by in vitro kinase assay which showed that NCI 748494/1 possessed promising inhibitory activity against c-Met kinase enzyme. Assessment of ADMET profiling, drug-likeness, drug score as well as docking simulation for the binding pose of that compound in the active site of c-Met kinase domain revealed that NCI 748494/1 could be considered as a promising drug lead. Based on target identification and validation, it was observed that there is structure similarity between NCI 748494/1 and the reported type II c-Met kinase inhibitor BMS-777607. Optimization of our lead NCI 748494/1 furnished newly synthesized 1,2,4-triazine derivatives based on well-established structure-activity relationships, whereas three compounds namely; 4d, 7a and 8c displayed excellent in vitro cytotoxicity against three c-Met addicted cancer cell lines; A549 (lung adenocarcinoma), HT-29 (colon cancer) and MKN-45 (gastric carcinoma); with IC50 values in the range 0.01-1.86 µM. In vitro c-Met kinase assay showed 8c to possess the highest c-Met kinase inhibition profile (IC50 = 4.31 µM). Docking of the active compounds in c-Met kinase active site revealed strong binding interactions comparable to the lead NCI 748494/1 and BMS-777607, suggesting that c-Met inhibition is very likely to be the mechanism of the antitumor effect of these derivatives.
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      PubDate: 2017-06-28T12:34:32Z
      DOI: 10.1016/j.bioorg.2017.06.009
  • Auspicious Role of the Steroidal Heterocyclic Derivatives as a Platform
           for Anti-cancer Drugs
    • Authors: Mohamed A. Tantawy; Mohamed S. Nafie; Gamal A. Elmegeed; Ibrahim A.I. Ali
      Abstract: Publication date: Available online 20 June 2017
      Source:Bioorganic Chemistry
      Author(s): Mohamed A. Tantawy, Mohamed S. Nafie, Gamal A. Elmegeed, Ibrahim A.I. Ali
      Steroids are polycyclic compounds that have a wide range of biological activities. They are bio-synthesized from cholesterol through a series of enzyme-mediated transformations, so they are highly lipophilic and readily enter most cells to interact with intracellular receptors, making them ideal vehicles for targeting a broad array of pathologies. New curative agents for cancers have been developed from several steroidal derivatives. Some biologically important properties of modified steroids are dependent on structural features of the steroid moiety and their side chains. Therefore, chemical derivatization of steroids provides a way to modify their function, and many structure–activity relationships have been confirmed by such synthetic modifications. Several studies demonstrate that steroidal heterocyclic derivatives can be effective in the prevention and treatment of many types of hormone-dependent cancers. The present review is a concise report on steroidal heterocyclic derivatives, with special emphasis on steroid heterocyclic derivatives with 5 membered rings or six-membered rings having interesting therapeutic potential as enzyme inhibitors and cytotoxic drugs to be used as candidates for anti-cancer drug development.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.006
  • Designing structural-motifs for the preparation of acylated proinsulin and
           their regiospecific conversion into insulin modified at Lys29 (K29)
    • Authors: Munir Ahmad; QurratulAnn Afza Gardner; Naeem Rashid; Muhammad Akhtar
      Abstract: Publication date: Available online 19 June 2017
      Source:Bioorganic Chemistry
      Author(s): Munir Ahmad, QurratulAnn Afza Gardner, Naeem Rashid, Muhammad Akhtar
      Eight proinsulin encoding genes were prepared and their translation products, when treated with a cocktail of trypsin and carboxypeptidase B, analyzed for the following features. One, their ability to undergo facile removal of the N-terminal linker, generating the phenylalanine residue destined to be the N-terminal of the B-chain of insulin, at a rate similar to that involved in the removal of the C-peptide. Two, processing of diarginyl insulin, produced in the latter process, by carboxypeptidase B then needed to be rapid to remove the two arginine residues, Three, both these operations were to be efficient whether the N-terminal methionine was acylated or not. Four, the proinsulin constructs needed to contain a minimum number of sites for acylation. The aforementioned features were monitored by mass spectrometry and the proinsulin derivative containing MRR at the N-terminal and K64 mutated to Q64, designated as MRR-(Q64) human proinsulin [MRR-(Q64) hpi] optimally fulfilled these requirements. The derivative was smoothly acylated with reagents of two chain lengths (acetyl and dodecanoyl) to give acetyl/dodecanoyl MRR-(Q64) hpi. Acetyl MRR-(Q64) hpi, using the cocktail of the two enzymes, was smoothly converted into, acetyl insulin. However, when dodecanoyl MRR-(Q64) hpi was processed with the above cocktail, carboxypeptidase B (whether from animal pancreas or recombinant) showed an unexpected specificity of acting on the K29-T30 bond of the insulin derivatives when K29 contained a large hydrophobic acyl group, generating dodecanoyl des-30 insulin.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.005
  • Oxovanadium(IV) complexes with Knoevenagel Schiff base condensate as
           impending chemotherapeutic agents: Synthesis, characterization, biological
           screening and anti-proliferative assay
    • Authors: Rajakkani Paulpandiyan; Natarajan Raman
      Abstract: Publication date: Available online 19 June 2017
      Source:Bioorganic Chemistry
      Author(s): Rajakkani Paulpandiyan, Natarajan Raman
      Two novel oxovanadium(IV) complexes [VOL1]SO4 (1) and [VOL2]SO4 (2) containing Knoevenagel condensate Schiff base ligand (L1/L2) have been synthesized and characterized by physical, spectral and analytical methods. These complexes are reported as ionic in nature on the basis of elemental composition and molar conductance, and possess square pyramidal geometry around the central metal ions. The binding interactions of (1) and (2) with calf thymus DNA (CT DNA) were explored by absorption spectrophotometric titration, cyclic voltammetry data and viscosity measurements. The calculated intrinsic binding constant values (Kb) for (1) and (2) obtained from UV-Vis absorption studies are 0.4×105 and 5.6×105 (M−1) respectively. These experimental results indicate that (1) and (2) are intercalative binders and avid binder to CT DNA with different affinities. These complexes exhibit significant oxidative cleavage of supercoiled plasmid (pUC18) DNA in the presence of activators. In particular, the in vitro antimicrobial efficacy of oxovanadium(IV) complexes reveal that they are more active than free ligands. Besides, the in vitro cytotoxic effect of the titled complexes were examined on a bundle of human tumor cell lines such as MCF-7 and HeLa cancerous cell lines by the MTT method. Interestingly, complex (2) exhibits more potent cytotoxic activity than the other complex and standard drug (cisplatin). The mode of cell death was assessed by Hoechst 33258 staining morphological studies.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.008
  • Synthesis and biological evaluation of indole derivatives as
           α-amylase inhibitor
    • Authors: Syahrul Imran; Muhammad Taha; Manikandan Selvaraj; Nor Hadiani Ismail; Sridevi Chigurupati; Jahidul Islam Mohammad
      Abstract: Publication date: Available online 19 June 2017
      Source:Bioorganic Chemistry
      Author(s): Syahrul Imran, Muhammad Taha, Manikandan Selvaraj, Nor Hadiani Ismail, Sridevi Chigurupati, Jahidul Islam Mohammad
      A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 values ranging between 1.66 – 2.65 μM. Nine compounds that are 1 (2.23 ± 0.01 μM), 8 (2.44 ± 0.12 μM), 10 (1.92 ± 0.12 μM), 12 (2.49 ± 0.17 μM), 13 (1.66 ± 0.09 μM), 17 (2.25 ± 0.1 μM), 18 (1.87 ± 0.25 μM), 20 (1.83 ± 0.63 μM), and 19 (1.97 ± 0.02 μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05 ± 0.29 μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.007
  • Design and environmentally benign synthesis of novel thiophene appended
           pyrazole analogues as anti-inflammatory and radical scavenging agents:
           crystallographic, in silico modeling, docking and SAR characterization
    • Authors: Malledevarapura Gurumurthy Prabhudeva; Srinivasan Bharath; Achutha Dileep Kumar; Shivalingegowda Naveen; Neratur Krishnappagowda Lokanath; Bantaganahalli Ningappa Mylarappa; Kariyappa Ajay Kumar
      Abstract: Publication date: Available online 16 June 2017
      Source:Bioorganic Chemistry
      Author(s): Malledevarapura Gurumurthy Prabhudeva, Srinivasan Bharath, Achutha Dileep Kumar, Shivalingegowda Naveen, Neratur Krishnappagowda Lokanath, Bantaganahalli Ningappa Mylarappa, Kariyappa Ajay Kumar
      Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal x-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.004
  • New 1,3,4-Oxadiazole/Oxime hybrids: Design, Synthesis, anti-inflammatory,
           COX inhibitory activities and Ulcerogenic liability.
    • Authors: Heba S. Abd-Ellah; Mohamed Abdel-Aziz; Mai E. Shoman; Eman A.M. Beshr; TamerS. Kaoud; Al-Shaimaa F.F. Ahmed
      Abstract: Publication date: Available online 15 June 2017
      Source:Bioorganic Chemistry
      Author(s): Heba S. Abd-Ellah, Mohamed Abdel-Aziz, Mai E. Shoman, Eman A.M. Beshr, TamerS. Kaoud, Al-Shaimaa F.F. Ahmed
      A series of new 1,3,4-oxadiazole/oxime hybrids were synthesized and designed as potent COX inhibitors. The prepared compounds were evaluated for their anti-inflammatory, antioxidant and ulcerogenic activities. The results indicated that the prepared compounds exhibited remarkable anti-inflammatory activity with (69.60- 109.60% of indomethacin activity) after 4h. In vitro COX inhibitory assay showed that compounds 6d and 7h are potent COX inhibitors with IC50 of (1.10-0.94) and (2.30-5.00) µM on both COX-1 and COX-2 respectively. Compound 7h was found to inhibit both COXs non-competitively with Ki values of 73 µM and 89 µM. Most of the tested compounds showed ulcer-free stomachs compared to indomethacin.
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      PubDate: 2017-06-21T12:11:37Z
      DOI: 10.1016/j.bioorg.2017.06.003
  • Synthesis of novel fenfuram-diarylether hybrids as potent succinate
           dehydrogenase inhibitors
    • Authors: Hong Jin; Jingya Zhou; Tao Pu; Aigui Zhang; Xuheng Gao; Ke Tao; Taiping Hou
      Abstract: Publication date: Available online 6 June 2017
      Source:Bioorganic Chemistry
      Author(s): Hong Jin, Jingya Zhou, Tao Pu, Aigui Zhang, Xuheng Gao, Ke Tao, Taiping Hou
      Twelve novel fenfuram-diarylether hybrids were designed, synthesized and characterized by 1H NMR and MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi by mycelial growth inhibition method. Most compounds showed significant antifungal effect on Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 1c exhibited the most potent antifungal effect on R. solani with an EC50 value of 0.242 mg/L, superior to the commercial fungicide boscalid (EC50 = 1.758 mg/L) and the lead fungicide fenfuram (EC50 = 7.691 mg/L). Molecular docking revealed that compound 1c featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 2-chlorophenyl group of compound 1c formed a π-π stacking with D/Tyr-128 and a Cl-π interaction with B/His-249, which made compound 1c more active than fenfuram against SDH.
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      PubDate: 2017-06-11T11:41:26Z
      DOI: 10.1016/j.bioorg.2017.06.002
  • Oxidative transformation of tunichromes - Model studies with
           1,2-dehydro-N-acetyldopamine and N-acetylcysteine
    • Authors: Qun F. Kuang; Adal Abebe; Jason Evans; Manickam Sugumaran
      Abstract: Publication date: Available online 1 June 2017
      Source:Bioorganic Chemistry
      Author(s): Qun F. Kuang, Adal Abebe, Jason Evans, Manickam Sugumaran
      Tunichromes are 1,2-dehydrodopa containing bioactive peptidyl derivatives found in blood cells of several tunicates. They have been implicated in metal sequestering, tunic formation, wound healing and defense reaction. Earlier studies conducted on these compounds indicate their extreme liability, high reactivity and easy oxidative polymerization. Their reactions are also complicated by the presence of multiple dehydrodopyl units. Since they have been invoked in crosslinking and covalent binding, to understand the reactivities of these novel compounds, we have taken a simple model compound that possess the tunichrome reactive group viz., 1,2-dehydro-N-acetyldopamine (Dehydro NADA) and examined its reaction with N-acetyl cysteine in presence of oxygen under both enzymatic and nonenzymatic conditions. Ultraviolet and visible spectral studies of reaction mixtures containing dehydro NADA and N-acetylcysteine in different molar ratios indicated the production of side chain and ring adducts of N-acetylcysteine to dehydro NADA. Liquid chromatography and mass spectral studies supported this contention and confirmed the production of several different products. Mass spectral analysis of these products show the potentials of dehydro NADA to form side chain adducts that can lead to polymeric products. This is the first report demonstrating the ability of dehydro dopyl units to form adducts and crosslinks with amino acid side chains.
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      PubDate: 2017-06-06T11:34:36Z
      DOI: 10.1016/j.bioorg.2017.05.013
  • Apoptotic Induction Mediated p53 Mechanism and Caspase-3 Activity by Novel
           Promising Cyanoacrylamide Derivatives in Breast Carcinoma
    • Authors: Magda F. Mohamed; Noha Samir; Aya Ali; Nawal Ahmed; Yassmen Ali; Sarah Aref; Omnia Hossam; Mervat S. Mohamed; Amr M. Abdelmoniem; Ismail A. Abdelhamid
      Abstract: Publication date: Available online 1 June 2017
      Source:Bioorganic Chemistry
      Author(s): Magda F. Mohamed, Noha Samir, Aya Ali, Nawal Ahmed, Yassmen Ali, Sarah Aref, Omnia Hossam, Mervat S. Mohamed, Amr M. Abdelmoniem, Ismail A. Abdelhamid
      A new five cyanoacrylamide derivatives were theoretically examined for their binding abilities to a protein model of apoptosis inhibitor proteins x-IAP and c-IAP1 using molecular modeling. The two compound 5a and 5b proved promising IAP antagonists, where they have good binding affinity toward the selected active domains. Anticancer activity of all derivatives was performed on different human cancer cell lines (HCT116, Caco2, and MCF7) as well as normal line (HBF4). Data revealed that breast carcinoma was more sensitive to our novels than other lines especially compounds 5a and 5b, but all derivatives lost their cytotoxic effect in case of Caco2 cell line and they showed low cytotoxic effect toward HCT116 cells except compound 3. The flow cytometric analysis revealed that the two compounds 5a and 5b induced apoptosis to 46.5% and 54.8% respectively, relative to control 8.06%. In addition, PCR results indicated that the two compounds 5a and 5b induced the expression of p53 gene and decreased induction of BCL2 (anti-apoptotic gene), while the two compounds have no effect on the protein expression of Caspase-9. By monitoring the presence of Caspase-3 which was a mean to detect apoptotic death in breast carcinoma, the two compounds have stimulated the induction of apoptosis by increasing the production of Caspase-3 protein. Finally, it was concluded that the two compounds 5b and 5a have the most promising anti-cancer activity against human breast carcinoma (MCF7), and it is believed that the anticancer activities of these two compounds were due to being the most effective in the inhibition of a member of IAPs groups, leading to activation of p53 gene and the Caspase-3 dependent apoptosis.
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      PubDate: 2017-06-06T11:34:36Z
      DOI: 10.1016/j.bioorg.2017.05.012
  • Comparison of seven structurally related coumarins on the inhibition of
           quorum sensing of Pseudomonas aeruginosa and Chromobacterium violaceum.
    • Authors: D'Almeida R.E; Molina R; Viola C; Luciardi M.C; Nieto C; Bardón A; Arena M.E.
      Abstract: Publication date: Available online 31 May 2017
      Source:Bioorganic Chemistry
      Author(s): D'Almeida R.E, Molina R, Viola C, Luciardi M.C, Nieto C, Bardón A, Arena M.E.
      Quorum sensing (QS) is a cell-to-cell signaling communication system that controls the virulence behavior of a broad spectrum of bacterial pathogens, participating also in the development of biofilms, responsible of the antibiotic ineffectiveness in many infections. Therefore, QS system is an attractive target for antimicrobial therapy. In this study, we compare the effect of seven structurally related coumarins against bacterial growth, biofilm formation and elastase activity of Pseudomonas aeruginosa. In addition, the anti-pathogenic capacity of the seven coumarins was evaluated on the wild type and the biosensor strain of Chromobacterium violaceum. The comparative study of coumarins showed that molecules with hydroxyl groups on the aromatic ring displayed higher activity on the inhibition of biofilm formation of P. aeruginosa over coumarins with substituents in positions 3 and 4 or without the double 3,4-bond. These 3 or 4-hydroxylated positions caused a decrease in the anti-biofilm activity obtained for coumarin. However, the hydroxyl group in position 3 of the pyrone ring was important for the inhibition of C. violaceum QS and elastolytic activity of P. aeruginosa. The effects observed were active independently of any effect on growth. According to our results, coumarin and its hydroxylated derivatives represent an interesting group of compounds to use as anti-virulence agents against the human pathogen P. aeruginosa.
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      PubDate: 2017-06-06T11:34:36Z
      DOI: 10.1016/j.bioorg.2017.05.011
  • Design, synthesis, immunocytochemistry evaluation, and molecular docking
           investigation of several 4-aminopyridine derivatives as potential
           neuroprotective agents for treating Parkinson’s disease
    • Authors: Shulin Li; Daiyan Wei; Zhuo Mao; Ligong Chen; Xilong Yan; Yang Li; Shengjie Dong; Donghua Wang
      Abstract: Publication date: Available online 31 May 2017
      Source:Bioorganic Chemistry
      Author(s): Shulin Li, Daiyan Wei, Zhuo Mao, Ligong Chen, Xilong Yan, Yang Li, Shengjie Dong, Donghua Wang
      Neuroprotection refers to the relative preservation of neuronal structure and function. Neuroprotective agents refer to substances that are capable of preserving brain function and structure. Currently, there are no neuroprotective agents available that can effectively relieve the progression of Parkinson’s disease. In this work, five novel 4-aminopyridine derivatives, including three amides and two ureas, were designed, synthesized, and evaluated using the rat PC12 mice pheochromocytoma cell line as an in vitro model. As well as human Rho kinase inhibitory experiment was performed. Among them, compounds 3, which exhibited high cell viability, low cytotoxicity and good efficacy of inhibition on α-synuclein, oxidation, inflammation and Rho kinase were profound as potential agents for Parkinson’s disease (PD).
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      PubDate: 2017-06-06T11:34:36Z
      DOI: 10.1016/j.bioorg.2017.05.010
  • Issue TOC
    • Abstract: Publication date: June 2017
      Source:Bioorganic Chemistry, Volume 72

      PubDate: 2017-05-22T12:00:17Z
  • Hetarylcoumarins: Synthesis and biological evaluation as potent
           α-glucosidase inhibitors
    • Authors: Faryal Chaudhry; Shahnaz Choudhry; Rahila Huma; Muhammad Ashraf; Mariya al-Rashida; Rubina Munir; Ramsha Sohail; Bakhat Jahan; Munawar Ali Munawar; Misbahul Ain Khan
      Abstract: Publication date: Available online 10 May 2017
      Source:Bioorganic Chemistry
      Author(s): Faryal Chaudhry, Shahnaz Choudhry, Rahila Huma, Muhammad Ashraf, Mariya al-Rashida, Rubina Munir, Ramsha Sohail, Bakhat Jahan, Munawar Ali Munawar, Misbahul Ain Khan
      In search of better α-glucosidase inhibitors, a series of novel hetarylcoumarins (3a-3j) were designed and synthesized through a facile multicomponent route where p-toluenesulfonic acid (PTSA) was explored as an efficient catalyst. These new scaffolds were further evaluated for their α-glucosidase inhibition potentials. All the derivatives exhibited good to excellent results which were comparable or even better than of standard drug acarbose. Of these compounds, a dihalogenated compound 3f was found to be the most effective one with IC50: 2.53 ± 0.002 µM. Molecular docking has predicted the plausible binding interactions of compounds 3f, 3g and 3j with α-glucosidase.
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      PubDate: 2017-05-12T09:14:12Z
      DOI: 10.1016/j.bioorg.2017.05.009
  • Efficient synthesis of novel dialkyl-3-cyanopropylphosphate derivatives
           and evaluation of their anticholinesterase activity
    • Authors: Iyadh Aouani; Badreddine Sellami; Karima Lahbib; Jean-François Cavalier; Soufiane Touil
      Abstract: Publication date: Available online 6 May 2017
      Source:Bioorganic Chemistry
      Author(s): Iyadh Aouani, Badreddine Sellami, Karima Lahbib, Jean-François Cavalier, Soufiane Touil
      Based on the broad spectrum of biological activities associated with organophosphates, a novel type of this class of compounds was synthesized, bearing a nitrile group, from the sodium alkoxide-catalyzed reaction of dialkylphosphites with γ-ketonitriles at 80 °C under solvent-free conditions. A reaction mechanism involving a phospha-Brook type rearrangement is proposed. Eight title compounds were investigated for their in vitro inhibitory potency and selectivity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman’s spectrophotometric method. The synthesized derivatives exhibited mostly a moderate activity against both cholinesterases. The IC50 values for BChE were in a smaller concentration range (5.96–23.35 µM) compared to those for AChE inhibition (9.61–53.74 µM). The diethyl-3-cyano-1-p-tolylpropylphosphate which displayed the higher dual inhibitory potency towards both cholinesterases could be considered as a potential candidate for developing new drugs to treat Alzheimer’s disease.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.008
  • Synthesis, molecular docking and anti-diabetic evaluation of
           2,4-thiazolidinedione based amide derivatives
    • Authors: Mohd. Javed Naim; Md. Jahangir Alam; Farah Nawaz; V.G.M. Naidu; Shams Aaghaz; Meeta Sahu; Nadeem Siddiqui; Ozair Alam
      Abstract: Publication date: Available online 6 May 2017
      Source:Bioorganic Chemistry
      Author(s): Mohd. Javed Naim, Md. Jahangir Alam, Farah Nawaz, V.G.M. Naidu, Shams Aaghaz, Meeta Sahu, Nadeem Siddiqui, Ozair Alam
      A series of thiazolidinedione based amide derivatives were designed, synthesized and docked against the PPARγ receptor target. 11 compounds from the series with good glide scores were selected for in vivo antidiabetic study based on streptozotocin induced diabetic rat model. It was observed that 4 compounds (6c, 6e, 6m & 6n) showed significantly good antidiabetic activity in comparison to rosiglitazone and pioglitazone as reference drugs. Compound 6c appeared as the most potent derivative in lowering blood glucose level and showed excellent interaction with SER 342, ILE 281, pi-pi interaction with ARG 288 and halogen bond interaction with LYS 367. Further, PPARγ transactivation and gene expression studies of compound 6c were carried out to investigate the possible mechanism of action through PPARγ modulation. Compound 6c exhibited 53.65% transactivation and elevated PPARγ gene expression by 2.1 folds. The biochemical parameters (AST, ALT and ALP levels) were found within the range with no noteworthy damage to liver.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.007
  • Synthesis, Biological Evaluation and Molecular Modeling Study of new
           (1,2,4-Triazole or 1,3,4-Thiadiazole)-methylthio- Derivatives of
           Quinazolin-4(3H)-one as DHFR Inhibitors
    • Authors: Yomna I. El-Gazzar; Hanan H. Georgey; Shahenda M. El-Messery; Heba A. Ewida; Ghada S. Hassan; Marwa M. Raafat; Menna A. Ewida; Hussein I. El-Subbagh
      Abstract: Publication date: Available online 4 May 2017
      Source:Bioorganic Chemistry
      Author(s): Yomna I. El-Gazzar, Hanan H. Georgey, Shahenda M. El-Messery, Heba A. Ewida, Ghada S. Hassan, Marwa M. Raafat, Menna A. Ewida, Hussein I. El-Subbagh
      A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value of 0.01 μM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC50 values of 25.4 and 9.5 μg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.04.019
  • Structure-based Rational Design of Self-inhibitory Peptides to Disrupt the
           Intermolecular Interaction between the Troponin Subunits C and I in
           Neuropathic Pain
    • Authors: Junmin Yu; Shilei Wang; Junjie Yu; Chuansheng Liu; Fenghe Xu; Shijie Wang; Yusheng Yi; Yanwei Yin
      Abstract: Publication date: Available online 3 May 2017
      Source:Bioorganic Chemistry
      Author(s): Junmin Yu, Shilei Wang, Junjie Yu, Chuansheng Liu, Fenghe Xu, Shijie Wang, Yusheng Yi, Yanwei Yin
      The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC–TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders. Molecular dynamics simulation and binding free energy analysis suggests that the switch peptide can interact with TnC in a structurally and energetically independent manner. Terminal truncation of the peptide results in a number of potent TnC binders with considerably simplified structure and moderately decreased activity relative to the native switch. We also employ fluorescence polarization assays to substantiate the computational findings; it is found that the rationally designed peptides exhibit moderate or high affinity to TnC with dissociation constants K D at micromolar level.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.004
  • PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their
           kinetic properties and molecular docking simulation
    • Authors: Duc Dat Le; Duc Hung Nguyen; Bing Tian Zhao; Su Hui Seong; Jae Sue Choi; Seok Kyu Kim; Jeong Ah Kim; Byung Sun Min; Mi Hee Woo
      Abstract: Publication date: Available online 2 May 2017
      Source:Bioorganic Chemistry
      Author(s): Duc Dat Le, Duc Hung Nguyen, Bing Tian Zhao, Su Hui Seong, Jae Sue Choi, Seok Kyu Kim, Jeong Ah Kim, Byung Sun Min, Mi Hee Woo
      Diabetes is one of the most popular worldwide diseases, regulated by the defects in insulin secretion, insulin action, or both. The overexpression of protein tyrosine phosphatase 1B (PTP1B) was found to down-regulate the insulin-receptor activation. PTP1B has been known as a strategy for the treatment of diabetes via the regulation of insulin signal transduction pathway. Herein, we investigated the PTP1B inhibitors isolated from natural sources. The chemical investigation of Selaginella tamariscina (Beauv.) Spring revealed seven unsaturated alkylyl phenols 1-7, four new selaginellins T-W 1-4 together with three known compounds 5-7 isolated from the aerial parts. The structures of the isolates were determined by spectroscopic techniques (1D/2D-NMR, MS, and CD). The inhibitory effects of these isolates on the PTP1B enzyme activity were investigated. Among them, compounds 2-7 significantly exhibited the inhibitory effects with the IC50 values ranging from 4.8 to 15.9 μM. Compound 1 moderately displayed the inhibitory activity with an IC50 of 57.9 μM. Furthermore, active compounds were discovered from their kinetic and molecular docking analysis. The results revealed that compounds 2 and 4-7 were mixed-competitive inhibitors, whereas compound 3 was a non-competitive inhibitor. This data confirm that these compounds exhibited potential inhibitory effect on the PTP1B enzyme activity.
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      PubDate: 2017-05-06T19:06:05Z
      DOI: 10.1016/j.bioorg.2017.05.001
  • Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with
           their protein tyrosine phosphatase and acetylcholinesterase inhibitory
    • Authors: Duc Hung Nguyen; U Min Seo; Bing Tian Zhao; Duc Dat Le; Su Hui Seong; Jae Sue Choi; Byung Sun Min; Mi Hee Woo
      Abstract: Publication date: Available online 30 April 2017
      Source:Bioorganic Chemistry
      Author(s): Duc Hung Nguyen, U Min Seo, Bing Tian Zhao, Duc Dat Le, Su Hui Seong, Jae Sue Choi, Byung Sun Min, Mi Hee Woo
      A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-D-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC50 values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC50 value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC50 values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.
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      PubDate: 2017-04-30T18:34:37Z
      DOI: 10.1016/j.bioorg.2017.04.017
  • Facile synthesis of fluoro, methoxy, and methyl substituted
           ferrocene-based urea complexes as potential therapeutic agents
    • Authors: Faiza Asghar; Amin Badshah; Bhajan Lal; Shumaila Zubair; Saira Fatima; Ian S. Butler
      Abstract: Publication date: Available online 29 April 2017
      Source:Bioorganic Chemistry
      Author(s): Faiza Asghar, Amin Badshah, Bhajan Lal, Shumaila Zubair, Saira Fatima, Ian S. Butler
      In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and 13C) NMR, AAS, Raman, and elemental analysis), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry), and in vitro biological assessment of nine new ferrocene-based ureas are reported. The desulphurization of ferrocenyl thioureas to the corresponding oxo analogues using aqueous sodium hydroxide and mercuric chloride led to the ferrocenyl ureas (F1-F9) in high yields. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of cytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin).
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      PubDate: 2017-04-30T18:34:37Z
      DOI: 10.1016/j.bioorg.2017.04.016
  • Fatty-monastrol derivatives and its cytotoxic effect against melanoma cell
    • Authors: Milene Medeiros de Moraes; Tamara Germani Marinho Treptow; Wystan Kreisly Othon Teixeira; Luciana Almeida Piovesan; Marcelo Gonçalves Montes D'Oca; Ana Paula de Souza Votto
      Abstract: Publication date: Available online 22 April 2017
      Source:Bioorganic Chemistry
      Author(s): Milene Medeiros de Moraes, Tamara Germani Marinho Treptow, Wystan Kreisly Othon Teixeira, Luciana Almeida Piovesan, Marcelo Gonçalves Montes D'Oca, Ana Paula de Souza Votto
      Melanoma is the most dangerous type of skin cancer due to the occurrence of metastases. This work is aimed at studying the effects of the insertion of palmitic and oleic acid chain into monastrol in the melanoma cell line, B16F10. Cells were treated with monastrol, palmitic-monastrol or oleic-monastrol for periods of 0, 24, 48 and 72 hours, and the cytotoxic effect was observed for palmitic-monastrol and oleic-monastrol after 24 hours. For monastrol the effects were observed in 48 hours on B16F10 cells, and in 24 hours for a non-tumour cell line, melan-a. In this cell line, fatty-monastrol derivatives were cytotoxic after 24 hours of exposure in the same concentrations as B16F10. However, oleic-monastrol inhibited cell growth at 20 µM only after 72 hours, in contrast to the B16F10 cell line, in which oleic-monastrol inhibited cell growth at 48 hours, showing that at least in this structural modification, melan-a was less sensitive than B16F10. The ability of compounds to induce apoptosis and/or necrosis was measured, and it was observed that monastrol induces apoptosis within 24 hours. However, the cells treated with fatty-monastrol derivatives did not remain adhered on the well plate after 3 hours of treatment. At this time point, these cells still emitted fluorescence indicating viable cells, suggesting a possible effect of palmitic- and oleic- monastrol in the adhesion proteins found on the cell membrane.
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      PubDate: 2017-04-24T11:49:45Z
      DOI: 10.1016/j.bioorg.2017.04.011
  • Synthesis of Alpha Amylase Inhibitors Based on Privileged Indole Scaffold
    • Authors: Tayyaba Noreen; Muhammad Taha; Syahrul Imran; Sridevi Chigurpati; Fazal Rahim; Manikandan Selvaraj; Nor Hadiani Ismail; Jahidul Islam Mohammad; Hayat Ullah; Muhammad Tariq javid; Faisal Nawaz; Maryam Irshad; Muhammad Ali
      Abstract: Publication date: Available online 21 April 2017
      Source:Bioorganic Chemistry
      Author(s): Tayyaba Noreen, Muhammad Taha, Syahrul Imran, Sridevi Chigurpati, Fazal Rahim, Manikandan Selvaraj, Nor Hadiani Ismail, Jahidul Islam Mohammad, Hayat Ullah, Muhammad Tariq javid, Faisal Nawaz, Maryam Irshad, Muhammad Ali
      Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential ranging between 9.28-599.0 µM when compared with standard acarbose having IC50 value 8.78 ± 0.16 µM. Six analogs, 25 (IC50 = 9.28 ± 0.153 µM), 22 (IC50 = 9.79 ± 0.43 µM), 4 (IC50 = 11.08 ± 0.357 µM), 1 (IC50 = 12.65 ± 0.169 µM), 8 (IC50 = 21.37 ± 0.07 µM) and 14 (IC50 = 43.21 ± 0.14 µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50 = 8.78 ± 0.16 µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.
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      PubDate: 2017-04-24T11:49:45Z
      DOI: 10.1016/j.bioorg.2017.04.010
  • Hydrolysis of the amide bond in histidine- and methionine-containing
           dipeptides promoted by pyrazine and pyridazine palladium(II)-aqua dimers:
           comparative study with platinum(II) analogues
    • Authors: Marija D. Živković; Snežana Rajković; Biljana Đ. Glišić; Nenad S. Drašković; Miloš I. Djuran
      Abstract: Publication date: Available online 17 April 2017
      Source:Bioorganic Chemistry
      Author(s): Marija D. Živković, Snežana Rajković, Biljana Đ. Glišić, Nenad S. Drašković, Miloš I. Djuran
      Two dinuclear palladium(II) complexes, [{Pd(en)Cl}2(μ-pz)](NO3)2 and [{Pd(en)Cl}2(μ-pydz)](NO3)2, have been synthesized and characterized by elemental microanalysis and spectroscopic (1H and 13C NMR, IR and UV-vis) techniques (en is ethylenediamine; pz is pyrazine and pydz is pyridazine). The square planar geometry of palladium(II) metal centers in these complexes has been predicted by DFT calculations. The chlorido complexes were converted into the corresponding aqua complexes, [{Pd(en)(H2O)}2(μ-pz)]4+ and [{Pd(en)(H2O)}2(μ-pydz)]4+, and their reactions with N-acetylated L-histidylglycine (Ac–L–His–Gly) and L-methionylglycine (Ac–L–Met–Gly) were studied by 1H NMR spectroscopy. The palladium(II)-aqua complexes and dipeptides were reacted in 1:1 molar ratio, and all reactions performed in the pH range 2.0 < pH < 2.5 in D2O solvent and at 37 °C. In the reactions of these complexes with Ac–L–His–Gly and Ac–L–Met–Gly dipeptides, the hydrolysis of the amide bonds involving the carboxylic group of both histidine and methionine amino acids occurs. The catalytic activities of the palladium(II)-aqua complexes were compared with those previously reported in the literature for the analogues platinum(II)-aqua complexes, [{Pt(en)(H2O)}2(μ-pz)]4+ and [{Pt(en)(H2O)}2(μ-pydz)]4+.
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      PubDate: 2017-04-24T11:49:45Z
      DOI: 10.1016/j.bioorg.2017.04.008
  • Synthesis, Crystal structure determination, biological screening and
           docking studies of N1-substituted derivatives of
           2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases
    • Authors: Nargis Sultana; Muhammad Sarfraz; Saba Tahir; Muhammad SafwanAkram; Abdul Sadiq; Umer Rashid; Muhammad Ilyas Tariq
      Abstract: Publication date: Available online 17 April 2017
      Source:Bioorganic Chemistry
      Author(s): Nargis Sultana, Muhammad Sarfraz, Saba Tahir, Muhammad SafwanAkram, Abdul Sadiq, Umer Rashid, Muhammad Ilyas Tariq
      Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N1-substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC50 values toward AChE in submicromolar range (0.8 µM and 0.6 µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase.
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      PubDate: 2017-04-24T11:49:45Z
      DOI: 10.1016/j.bioorg.2017.04.009
  • Synthesis and biological evaluation of benzimidazole derivatives as the
           G9a Histone Methyltransferase inhibitors that induce autophagy and
           apoptosis of breast cancer cells
    • Authors: Jin Zhang; Dahong Yao; Yingnan Jiang; Jian Huang; Shilin Yang; Jinhui Wang
      Abstract: Publication date: Available online 17 April 2017
      Source:Bioorganic Chemistry
      Author(s): Jin Zhang, Dahong Yao, Yingnan Jiang, Jian Huang, Shilin Yang, Jinhui Wang
      G9a (also known as KMT1C or EHMT2) is initially identified as a H3K9 methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. It is overexpressed in various human cancers and employed as a promising target in cancer therapy. We discovered a benzoxazole scaffold through virtual high-throughput screening, and designed, synthesized 24 derivatives and investigated for inhibition of G9a. After several rounds of kinase and anti-proliferative activity screening, we discovered a potent G9a antagonist (GA001) with an IC50 value of 1.32 μM that could induce autophagy via AMPK in MCF7 cells. In addition, we found high concentration of GA001 could induce apoptosis via p21-Bim signal cascades in MCF7 cells. Our results highlight a new approach for the development of a novel drug targeting G9a with a potential to induce autophagy and apoptosis for future breast cancer therapy.
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      PubDate: 2017-04-24T11:49:45Z
      DOI: 10.1016/j.bioorg.2017.04.005
  • Design, Synthesis and Biological Activity of
           3-Oxoamino-benzenesulfonamides as Selective and Reversible LSD1 Inhibitors
    • Authors: Jiayue Xi; Siyuan Xu; Liming Wu; Tianfang Ma; Rongfeng Liu; Yu-Chih Liu; Dawei Deng; Yueqing Gu; Jinpei Zhou; Fei Lan; Xiaoming Zha
      Abstract: Publication date: Available online 13 April 2017
      Source:Bioorganic Chemistry
      Author(s): Jiayue Xi, Siyuan Xu, Liming Wu, Tianfang Ma, Rongfeng Liu, Yu-Chih Liu, Dawei Deng, Yueqing Gu, Jinpei Zhou, Fei Lan, Xiaoming Zha
      Lysine specific demethylase 1 (LSD1) is a flavin-dependent amine oxidase that selectively removes one or two methyl groups from H3 at Lys4 and is recognized as a promising therapeutic target for cancer and other diseases. Here, a series of 3-oxoamino-benzenesulfonamides were synthesized and evaluated for their inhibitory activity against LSD1. Compounds 7b and 7h showed the most potent inhibition with the IC50 values of 9.5 and 6.9 μM, respectively. Furthermore, the LSD1 inhibition of 7b and 7h were reversible and selective. Docking study presented the possible binding mode between 7b, 7h and the LSD1 active site. Taken together, 3-oxoamino-benzenesulfonamides may represent a new class of reversible LSD1 inhibitors and 7b and 7h were two hit compounds deserved further structural optimization.
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      PubDate: 2017-04-17T15:47:15Z
      DOI: 10.1016/j.bioorg.2017.04.006
  • A biphenyl derivative from the twigs of Caenomeles speciosa
    • Authors: Won Se Suh; Kyoung Jin Park; Dong Hyun Kim; Lalita Subedi; Sun Yeou Kim; Sang Un Choi; Kang Ro Lee
      Abstract: Publication date: Available online 11 April 2017
      Source:Bioorganic Chemistry
      Author(s): Won Se Suh, Kyoung Jin Park, Dong Hyun Kim, Lalita Subedi, Sun Yeou Kim, Sang Un Choi, Kang Ro Lee
      In our continuing search for bioactive constituents of Korean medicinal sources, we investigated an 80% MeOH extract of the twigs of Chaenomeles speciosa. Column chromatographic purification of the CHCl3 fraction resulted in the isolation of a new biphenyl derivative (1), along with four known biphenyl compounds (2-5) and six triterpenes (6-11). The chemical structure of the new compound was determined on the basis of spectroscopic analyses including 1D and 2D NMR data. Among isolates, compound 3 exhibited potent cytotoxic activities against SK-OV-3, SK-MEL-2, and XF498 cell lines (IC50 = 5.91, 4.22, and 6.28 μM, respectively). Also, Compounds 9 and 10 showed strong anti-neuroinflammatory activities (IC50 2.38, and 6.70 μM, respectively).

      PubDate: 2017-04-17T15:47:15Z
      DOI: 10.1016/j.bioorg.2017.04.003
  • New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives:
           design, synthesis and biological evaluation as potential anti-inflammatory
           and analgesic agents
    • Authors: Khaled R.A. Abdellatif; Wael A.A. Fadaly
      Abstract: Publication date: Available online 9 April 2017
      Source:Bioorganic Chemistry
      Author(s): Khaled R.A. Abdellatif, Wael A.A. Fadaly
      A new series of 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives 10a-h was designed and synthesized for evaluation as selective COX-2 inhibitors, anti-inflammatory agents and as analgesic agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compounds 10a, 10b, 10e and 10f were the most COX-2 selective compounds (S.I. = 10.76, 10.87, 8.69 and 9.14 respectively), the most potent anti-inflammatory derivatives (ED50 = 65.7, 60.2, 76.3 and 107.4 μmol/kg respectively) in comparison with Celecoxib (COX-2 S.I. = 8.61, ED50 = 82.2 μmol/kg) and were less ulcerogenic (ulcer indexes = 1.22 – 3.02) than Ibuprofen (ulcer index = 20.25) and comparable to Celecoxib (ulcer index = 2.93). The four derivatives (10a, 10b, 10e and 10f) showed considerable analgesic activities which are clearly parallel to their anti-inflammatory activities.
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      PubDate: 2017-04-10T15:30:02Z
      DOI: 10.1016/j.bioorg.2017.04.002
  • Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives
           possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor
           tyrosine kinase inhibitors
    • Authors: Weijie Gu; Yuxuan Dai; Hao Qiang; Wei Shi; Chen Liao; Fangnuo Zhao; Wenlong Huang; Hai Qian
      Abstract: Publication date: Available online 8 April 2017
      Source:Bioorganic Chemistry
      Author(s): Weijie Gu, Yuxuan Dai, Hao Qiang, Wei Shi, Chen Liao, Fangnuo Zhao, Wenlong Huang, Hai Qian
      In our efforts to develop novel dual c-Met/VEGFR-2 inhibitors as potential anticancer agents, a series of 2-substituted-4-(2-fluorophenoxy) pyridine derivatives bearing pyrazolone scaffold were designed and synthesized. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2, especially compound 9h, 12b and 12d. Based on the further enzyme assay in vitro, compound 12d was considered as the most promising one, the IC50 values of which were 0.11 μM and 0.19 μM for c-Met and VEGFR-2, respectively. Further molecular docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, indicating that 12d was a potential compound for cancer therapy deserving further study.
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      PubDate: 2017-04-10T15:30:02Z
      DOI: 10.1016/j.bioorg.2017.04.001
  • New hybrid molecules combining benzothiophene or benzofuran with rhodanine
           as dual COX-1/2 and 5-LOXinhibitors: Synthesis, biological evaluation and
           docking study
    • Authors: Mostafa M.M. El-Miligy; Aly A. Hazzaa; Hanan El-Messmary; Rasha A. Nassra; Soad A.M. El-Hawash
      Abstract: Publication date: Available online 31 March 2017
      Source:Bioorganic Chemistry
      Author(s): Mostafa M.M. El-Miligy, Aly A. Hazzaa, Hanan El-Messmary, Rasha A. Nassra, Soad A.M. El-Hawash
      New molecular hybrids combining benzothiophene or its bioisostere benzofuran with rhodanine were synthesized as potential dual COX-2/5-LOX inhibitors. The benzothiophene or benzofuran scaffold was linked at position -2 with rhodanine which was further linked to various anti-inflammatory pharmacophores so as to investigate the effect of such molecular variation on the anti-inflammatory activity. The target compounds were evaluated for their in vitro COX/LOX inhibitory activity. The results revealed that, compound 5h exhibited significant COX-2 inhibition higher than celecoxib. Furthermore, compounds 5a, 5f and 5i showed COX-2 inhibitory activity comparable to celecoxib. Compound 5h showed selectivity index SI = 5.1 which was near to that of celecoxib (SI = 6.7). Compound 5h displayed LOX inhibitory activity twice that of meclofenamate sodium. Moreover, compounds 5a, 5e and 5f showed significant LOX inhibitory activity higher than that of meclofenamate sodium. Compound 5h was screened for its in vivo anti-inflammatory activity using formalin-induced paw edema and gastric ulcerogenic activity tests. The results revealed that, it showed in vivo decrease in formalin-induced paw edema volume higher than celecoxib. It also displayed gastrointestinal safety profile as celecoxib. The biological results were also consistent with the docking studies at the active sites of the target enzymes COX-2 and 5-LOX. Also, compound 5h showed physicochemical, ADMET, and drug-like properties within those considered adequate for a drug candidate.
      Graphical abstract image

      PubDate: 2017-04-03T15:08:13Z
      DOI: 10.1016/j.bioorg.2017.03.012
  • Carbohydrazones as New Class of Carbonic Anhydrase Inhibitors: Synthesis,
           Kinetics, and Ligand Docking Studies
    • Authors: Sarosh Iqbal; Muhammad Saleem; M. Kamran Azim; Muhammad Taha; Uzma Salar; Khalid Mohammed Khan; Shahnaz Perveen; M. Iqbal Choudhary
      Abstract: Publication date: Available online 30 March 2017
      Source:Bioorganic Chemistry
      Author(s): Sarosh Iqbal, Muhammad Saleem, M. Kamran Azim, Muhammad Taha, Uzma Salar, Khalid Mohammed Khan, Shahnaz Perveen, M. Iqbal Choudhary
      Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50 = 1.33 ± 0.01 µM), 2 (IC50 = 1.85 ± 0.24 µM), 3 (IC50 = 1.37 ± 0.06 µM), and 9 (IC50 = 1.46 ± 0. 12 µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50 = 1.86 ± 0.03 µM). Moreover, compounds 4 (IC50 = 2.32 ± 0.04 µM), 5 (IC50 = 3.96 ± 0.35 µM), 7 (IC50 = 2.33 ± 0.02 µM), and 8 (IC50 = 2.67 ± 0.01 µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
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      PubDate: 2017-04-03T15:08:13Z
      DOI: 10.1016/j.bioorg.2017.03.014
  • Novel Quinuclidinone Derivatives Induced Apoptosis in Human Breast Cancer
           via Targeting P53
    • Authors: Ahmed Malki; Rasha Y. Elbayaa; Omnia Ali; Ahmed Sultan; Amal M. Youssef
      Abstract: Publication date: Available online 22 March 2017
      Source:Bioorganic Chemistry
      Author(s): Ahmed Malki, Rasha Y. Elbayaa, Omnia Ali, Ahmed Sultan, Amal M. Youssef
      Small molecules that can target human cancers have been highly sought to increase the anticancer efficacy, the present work describes the design and synthesis of novel series of five quinuclidinone derivatives (2a-2e). Their anticancer activities were investigated against breast cancer cells MCF-7, MDA-MB-231 breast cancer cells harboring mutant p53 and normal breast counterpart MCF-12a. Derivative 2e reduced proliferation of MCF-7 and MCF-12a while it has no effect on MDA-MB-231. Derivative 2e induced apoptosis in MCF-7 cells which is further confirmed by TUNEL assay and it reduced the percentage of cell in G2/M phase as confirmed by increased expression of cyclin B and reduced expression of cyclin D1. Derivative 2e reduced expression levels of Mdm2, Akt and ERK1/2 by and increased expression level of p53. Moreover, the apoptosis induction by 2e was also inhibited by PFT-α as evidenced by non-significant induction of apoptosis after treatment of MCF-7 cells with both derivative 2e and PFT-α. In addition, docking study reveals that derivative 2e has a binding pattern close to the pattern observed in the structure of the lead fragment 5,6-dimethoxy-2-methylbenzothiazole bound to T-p53C-Y220C. The above findings demonstrate that derivative 2e induces apoptosis in MCF-7 cells via targeting p53 which merits further development.
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      PubDate: 2017-03-26T17:16:55Z
      DOI: 10.1016/j.bioorg.2017.03.010
  • Design, synthesis, docking studies and biological evaluation of novel
           chalcone derivatives as potential histone deacetylase inhibitors
    • Authors: Mamdouh F.A. Mohamed; Montaser Sh.A. Shaykoon; Mostafa H. Abdelrahman; Bakheet E.M. Elsadek; Ahmed S. Aboraia; Gamal El-Din A.A. Abuo-Rahma
      Abstract: Publication date: Available online 19 March 2017
      Source:Bioorganic Chemistry
      Author(s): Mamdouh F.A. Mohamed, Montaser Sh.A. Shaykoon, Mostafa H. Abdelrahman, Bakheet E.M. Elsadek, Ahmed S. Aboraia, Gamal El-Din A.A. Abuo-Rahma
      A group of novel chalcone derivatives comprising hydroxamic acid or 2-aminobenzamide group as zinc binding groups (ZBG) were synthesized. The structure of the prepared compounds was fully characterized by IR, NMR and elemental microanalyses. Most of the tested compounds displayed strong to moderate HDAC inhibitory activity. Some of these compounds showed potent anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines. In particular, compounds 4a and 4b exhibited significant anti-proliferative activity against the three cell lines compared to SAHA as reference drug and displayed promising profile as anti-tumor candidates. The results indicated that these chalcone derivatives could serve as a promising lead compounds for further optimization as antitumor agents.
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      PubDate: 2017-03-20T17:07:21Z
      DOI: 10.1016/j.bioorg.2017.03.005
  • Synthesis, in vitro evaluation and molecular docking studies of novel
           amide linked triazolyl glycoconjugates as new inhibitors of α-glucosidase
    • Authors: Shyam Ji Gupta; Samrat Dutta; Rahul Gajbhiye; Parasuraman Jaisankar; Asish Kumar Sen
      Abstract: Publication date: Available online 18 March 2017
      Source:Bioorganic Chemistry
      Author(s): Shyam Ji Gupta, Samrat Dutta, Rahul Gajbhiye, Parasuraman Jaisankar, Asish Kumar Sen
      A series of N-substituted amide linked triazolyl β-D-glucopyranoside derivatives (4a-l) were synthesized and their in vitro inhibitory activity against yeast α-glucosidase enzyme [EC.] was assessed. Compounds 4e (IC50=156.06 µM), 4f (IC50=147.94 µM), 4k (IC50 =127.71 µM) and 4l (IC50 =121.33 µM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC50=130.98 µM) under the same in vitro experimental conditions. Kinetic study showed that both 4e and 4f inhibit the enzyme in a competitive manner with p-nitrophenyl α-D-glucopyranoside as substrate. Molecular docking studies of 4e, 4f, 4k and 4l were also carried out using homology model of α-glucosidase to find out the binding modes responsible for the inhibitory activity. This study revealed that the binding affinity of compounds 4e, 4f, 4k and 4l for α-glucosidase were -8.2, -8.6, -8.3 and -8.5 kcal/mol respectively, compared to that of acarbose (-8.9 kcal/mol). The results suggest that the N-substituted amide linked triazole glycoconjugates can reasonably mimic the substrates for the yeast α-glucosidase.
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      PubDate: 2017-03-20T17:07:21Z
      DOI: 10.1016/j.bioorg.2017.03.006
  • Synthesis, in vitro antiproliferative activity and kinase profile of new
           benzimidazole and benzotriazole derivatives
    • Authors: Konrad Chojnacki; Patrycja Wińska; Katarzyna Skierka; Monika Wielechowska; Maria Bretner
      Abstract: Publication date: Available online 16 March 2017
      Source:Bioorganic Chemistry
      Author(s): Konrad Chojnacki, Patrycja Wińska, Katarzyna Skierka, Monika Wielechowska, Maria Bretner
      Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with Ki value in the range of 1.96 – 0.91 μM, respectively. New TBBi derivatives 2, 3, 5 and 9 have demonstrated the EC50, in the range of 12-25μM and 13-29 μM respectively towards CCRF-CEM and MCF-7 cells. Derivatives TBBi decreased viability of cancer cells more efficiently than BALB cells and the biggest differences were observed for the azide substituted compounds 3 and 5. The effect of the most active compounds on the activity of eight off-target kinases was evaluated. Inhibitory efficiency of CK2-mediated p65 phosphorylation was demonstrated for the TBBi and compound 12.
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      PubDate: 2017-03-20T17:07:21Z
      DOI: 10.1016/j.bioorg.2017.02.017
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