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  Subjects -> CHEMISTRY (Total: 891 journals)
    - ANALYTICAL CHEMISTRY (55 journals)
    - CHEMISTRY (621 journals)
    - CRYSTALLOGRAPHY (21 journals)
    - ELECTROCHEMISTRY (28 journals)
    - INORGANIC CHEMISTRY (45 journals)
    - ORGANIC CHEMISTRY (51 journals)
    - PHYSICAL CHEMISTRY (70 journals)

CHEMISTRY (621 journals)                  1 2 3 4 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 14)
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: 43)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 21)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 26)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 41)
ACS Nano     Full-text available via subscription   (Followers: 273)
ACS Photonics     Full-text available via subscription   (Followers: 14)
ACS Symposium Series     Full-text available via subscription  
ACS Synthetic Biology     Full-text available via subscription   (Followers: 24)
Acta Chemica Iasi     Open Access   (Followers: 5)
Acta Chimica Slovaca     Open Access   (Followers: 2)
Acta Chimica Slovenica     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: 7)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 6)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 6)
Advanced Functional Materials     Hybrid Journal   (Followers: 57)
Advanced Science Focus     Free   (Followers: 5)
Advances in Chemical Engineering and Science     Open Access   (Followers: 66)
Advances in Chemical Science     Open Access   (Followers: 18)
Advances in Chemistry     Open Access   (Followers: 21)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19)
Advances in Drug Research     Full-text available via subscription   (Followers: 23)
Advances in Environmental Chemistry     Open Access   (Followers: 5)
Advances in Enzyme Research     Open Access   (Followers: 10)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 25)
Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 16)
Advances in Polymer Science     Hybrid Journal   (Followers: 43)
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: 6)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 3)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 64)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 17)
American Journal of Chemistry     Open Access   (Followers: 30)
American Journal of Plant Physiology     Open Access   (Followers: 11)
American Mineralogist     Hybrid Journal   (Followers: 15)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 165)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 243)
Annales UMCS, Chemia     Open Access  
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 5)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 9)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 13)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal   (Followers: 2)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 9)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 31)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 2)
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access  
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 350)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 10)
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: 2)
Biomacromolecules     Full-text available via subscription   (Followers: 21)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 7)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 128)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 84)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 2)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 6)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 71)
Catalysis for Sustainable Energy     Open Access   (Followers: 8)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 7)
Catalysis Science and Technology     Free   (Followers: 8)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 10)
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: 18)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 73)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 26)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 22)
Chemical Reviews     Full-text available via subscription   (Followers: 192)
Chemical Science     Open Access   (Followers: 24)
Chemical Technology     Open Access   (Followers: 24)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 56)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 24)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Biology     Full-text available via subscription   (Followers: 32)
Chemistry & Industry     Hybrid Journal   (Followers: 7)
Chemistry - A European Journal     Hybrid Journal   (Followers: 164)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 16)
Chemistry and Materials Research     Open Access   (Followers: 21)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 255)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 19)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 1)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 14)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 11)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 11)
Chromatographia     Hybrid Journal   (Followers: 24)
Chromatography     Open Access   (Followers: 2)
Chromatography Research International     Open Access   (Followers: 6)
Clay Minerals     Full-text available via subscription   (Followers: 10)
Cogent Chemistry     Open Access   (Followers: 1)
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 11)
Colloids and Interfaces     Open Access  
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 6)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 22)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Communications Chemistry     Open Access  
Composite Interfaces     Hybrid Journal   (Followers: 7)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 1)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 11)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 10)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Corrosion Series     Full-text available via subscription   (Followers: 6)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Croatica Chemica Acta     Open Access  
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
CrystEngComm     Full-text available via subscription   (Followers: 13)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Chromatography     Hybrid Journal  
Current Green Chemistry     Hybrid Journal  
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Microwave Chemistry     Hybrid Journal  
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 14)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 69)
Current Trends in Biotechnology and Chemical Research     Open Access   (Followers: 3)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  

        1 2 3 4 | Last

Journal Cover
Bioorganic Chemistry
Journal Prestige (SJR): 0.85
Citation Impact (citeScore): 4
Number of Followers: 10  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0045-2068 - ISSN (Online) 1090-2120
Published by Elsevier Homepage  [3163 journals]
  • Targeting oncogenic transcriptional corepressor Nac1 POZ domain with
           conformationally constrained peptides by cyclization and stapling
    • Authors: Tao Wu; Ping He; Wei Wu; Yingli Chen; Fenglin Lv
      Pages: 1 - 10
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Tao Wu, Ping He, Wei Wu, Yingli Chen, Fenglin Lv
      The oncogenic transcriptional corepressor Nac1 contains a conserved POZ protein–protein interaction module that mediates homodimerization or heterodimerization with itself or other POZ proteins. The dimerization has been recognized as an attractive target for cancer therapy. Here, we attempted to (i) discover those potential binding partners of Nac1 in the human genome, (ii) derive key peptide segments from the complex interface of Nac1 with its putative partners, and (iii) improve the peptide binding affinity to Nac1 POZ domain. In the procedure, Nac1 POZ dimerization with 136 human POZ domains was modeled, simulated and analyzed at atomic level to elucidate structural basis, energetic property and dynamics behavior. Two hotspot regions, namely α1-helix and α2/α3-hairpin, at the dimerization interface were identified that are responsible for stabilizing the formed POZ–POZ dimer complexes. The α1-helix and α2/α3-hairpin were stripped from the interface to derive their respective isolated SIP peptides, which, however, exhibited a large flexibility and intrinsic disorder in free state, and thus would incur a considerable penalty upon rebinding to Nac1 POZ domain. By carefully examining the natively folded structures of α1-helix and α2/α3-hairpin in protein context and their interaction modes with the domain, we rationally designed a hydrocarbon bridge and a disulfide bond separately for the two peptides in order to constrain their conformational flexibility in free state, thus largely minimizing the flexibility penalty. Consequently, three α1-helix peptides derived from Nac1, Miz1 and Slx4 were stapled by all-hydrocarbon bridge, while four α2/α3-hairpin peptides derived from Nac1, Bacd1, Klh28 and Mynn were cyclized by disulfide bond. Binding affinity analysis revealed that, as designed, these peptides were converted from non- or weak binders to moderate or good binders of Nac1 POZ domain upon the stapling and cyclization.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.024
      Issue No: Vol. 80 (2018)
       
  • Imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazinone as a new scaffold of
           DHFR inhibitors: Synthesis, biological evaluation and molecular modeling
           study
    • Authors: Menna A. Ewida; Dalal A. Abou El Ella; Deena S. Lasheen; Heba A. Ewida; Yomna I. El-Gazzar; Hussein I. El-Subbagh
      Pages: 11 - 23
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Menna A. Ewida, Dalal A. Abou El Ella, Deena S. Lasheen, Heba A. Ewida, Yomna I. El-Gazzar, Hussein I. El-Subbagh
      New series of thiazolo[4,5-d]pyridazin and imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazin analogues were designed, synthesized and evaluated for their invitro DHFR inhibition and antitumor activity. Compounds 13 and 43 proved to be DHFR inhibitors with IC50 0.05 and 0.06 μM, respectively. 43 proved lethal to OVCAR-3 Ovarian cancer and MDA-MB-435 Melanoma at IC50 0.32 and 0.46 μM, respectively. The active compounds formed hydrogen bond at DHFR binding site between N1-nitrogen of the pyridazine ring with Glu30; the carbonyl group with Trp24, Arg70 or Lys64; π-cation interaction with Arg22 and π-π interaction with Phe31 residues. Ring annexation of the active 1,3-thiazole ring analogue 13 into the bicyclic thiazolo[4,5-d]pyridazine (18,19) or imidazo[2,1-b]thiazoles (23–25) decreased the DHFR inhibition activity; while the formation of the tricyclic imidazo[2′,1′:2,3]-thiazolo[4,5-d]pyridazine (43–54) increased potency. The obtained model could be useful for the development of new class of DHFR inhibitors.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.025
      Issue No: Vol. 80 (2018)
       
  • Benzimidazole scaffold based hybrid molecules for various inflammatory
           targets: Synthesis and evaluation
    • Authors: Gaganpreet Kaur; Om Silakari
      Pages: 24 - 35
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Gaganpreet Kaur, Om Silakari
      Designing of hybrid drugs with specific multitarget profile is a promising line of attack against inflammation. In light of this, a series of benzimidazole scaffold based hybrid molecules were designed by integrating benzimidazoles (containing pharmacophoric elements for COXs and LOXs inhibitors) with phthalimide subunit of thalidomide (pharmacophore element for TNF-α inhibitor) under one construct via molecular hybridization strategy. The designed molecules were synthesized and evaluated for their inhibitory activity against COXs (COX-1, COX-2), LOXs (5-LOX, 15-LOX) enzymes as well as TNF-α inhibitory effect. The results revealed that, compounds (3a–l) obtained showed inhibition in submicromolar range against COXs and LOXs targets whereas milder inhibitory activity was obtained against lipopolysaccharides (LPS)-induced TNF-α secretion by murine macrophage-like cells (RAW264.7). Within this class of compounds, 3j emerged as having alluring multiple inhibitory effects on set of COX-1/2 and 5-/15-LOX enzymes (COX-1 IC50 = 9.85 µM; COX-2 IC50 = 1.00 µM; SI = 9.85; 5-LOX IC50 = 0.32 µM; 15-LOX IC50 = 1.02 µM) in conjunction with a good anti-inflammatory and analgesic activities. Additionally, compound 3j showed gastrointestinal safety with reduced lipid peroxidation. Docking results of compound 3j with COX-2 and 5-LOX were also consistent with the in vivo anti-inflammatory results.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.014
      Issue No: Vol. 80 (2018)
       
  • Synthesis, α-amylase inhibitory potential and molecular docking study
           of indole derivatives
    • Authors: Muhammad Taha; Mohd Syukri Baharudin; Nor Hadiani Ismail; Syahrul Imran; Muhammad Naseem Khan; Fazal Rahim; Manikandan Selvaraj; Sridevi Chigurupati; Muhammad Nawaz; Faiza Qureshi; Shantini Vijayabalan
      Pages: 36 - 42
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Muhammad Taha, Mohd Syukri Baharudin, Nor Hadiani Ismail, Syahrul Imran, Muhammad Naseem Khan, Fazal Rahim, Manikandan Selvaraj, Sridevi Chigurupati, Muhammad Nawaz, Faiza Qureshi, Shantini Vijayabalan
      In search of potent α-amylase inhibitor we have synthesized eighteen indole analogs (1–18), characterized by NMR and HR-EIMS and screened for α-amylase inhibitory activity. All analogs exhibited a variable degree of α-amylase inhibition with IC50 values ranging between 2.031 ± 0.11 and 2.633 ± 0.05 μM when compared with standard acarbose having IC50 values 1.927 ± 0.17 μM. All compounds showed good α-amylase inhibition. Compound 14 was found to be the most potent analog among the series. Structure-activity relationship has been established for all compounds mainly based on bringing about the difference of substituents on phenyl ring. To understand the binding interaction of the most active analogs molecular docking study was performed.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.021
      Issue No: Vol. 80 (2018)
       
  • Cytoprotective and antioxidant properties of organic selenides for the
           myelin-forming cells, oligodendrocytes
    • Authors: Saad Shaaban; Dominique Vervandier-Fasseur; Pierre Andreoletti; Amira Zarrouk; Philippe Richard; Amr Negm; Georg Manolikakes; Claus Jacob; Mustapha Cherkaoui-Malki
      Pages: 43 - 56
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Saad Shaaban, Dominique Vervandier-Fasseur, Pierre Andreoletti, Amira Zarrouk, Philippe Richard, Amr Negm, Georg Manolikakes, Claus Jacob, Mustapha Cherkaoui-Malki
      Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activity relationship to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. Collectively, we present new organoselenide compounds with cytoprotective and antioxidant properties that can be considered as promising drug candidates for myelin diseases.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.019
      Issue No: Vol. 80 (2018)
       
  • Characterization of inhibitory constituents of NO production from Catalpa
           ovata using LC-MS coupled with a cell-based assay
    • Authors: Sangmin Park; Hyeji Shin; Yeeun Park; Ilgyu Choi; Byoungduck Park; Ki Yong Lee
      Pages: 57 - 63
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Sangmin Park, Hyeji Shin, Yeeun Park, Ilgyu Choi, Byoungduck Park, Ki Yong Lee
      An effective screening method for inhibitors of NO production in natural products using LC-QTOF MS/MS coupled with a cell-based assay was proposed. The ethyl acetate fraction of Catalpa ovata exhibited a strong inhibitory effect on NO production in lipopolysaccharide-induced BV2 microglia cells. We attempted to identify the active constituents of C. ovata by using LC-QTOF MS/MS coupled with a cell-based assay. Peaks at approximately 14–15 min on the MS chromatogram were estimated to be the bioactive constituents. A new iridoid compound, 6-O-trans-feruloyl-3β-hydroxy-7-deoxyrehamaglutin A (4), and nine known compounds (1–3, 5–10) were isolated from the ethyl acetate fraction of C. ovata by repeated column chromatography. Compounds 3, 4, 5, 7, and 8 significantly attenuated lipopolysaccharide-stimulated NO production in BV2 cells. Our results indicate that LC-QTOF MS/MS coupled with a cell-based NO production inhibitory assay successfully predicted active compounds without a time-consuming isolation process.
      Graphical abstract image

      PubDate: 2018-06-03T13:51:49Z
      DOI: 10.1016/j.bioorg.2018.05.023
      Issue No: Vol. 80 (2018)
       
  • Discovery of dihydrobenzofuran neolignans from Rubus ideaus L. with
           enantioselective anti-Aβ1–42 aggregation activity
    • Authors: Le Zhou; Jie Wang; Rui Guo; Bin Lin; Xiao-Bo Wang; Xiao-Xiao Huang; Shao-Jiang Song
      Pages: 64 - 69
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Le Zhou, Jie Wang, Rui Guo, Bin Lin, Xiao-Bo Wang, Xiao-Xiao Huang, Shao-Jiang Song
      Four new dihydrobenzofuran neolignans 1a/1b and 2a/2b were isolated from the fruit of Rubus ideaus. 1a/1b and 2a/2b as two pairs of enantiomers were separated on a chiral chromatographic column. Their structures were determined using a suite of techniques including 1D and 2D NMR, HRESIMS, together with theoretical electronic circular dichroism (ECD) calculation. All compounds were evaluated for their inhibition of self-induced Aβ 1–42 aggregation. Compounds 1b and 2a exhibited optimal Aβ 1–42 aggregation inhibition capability, with an inhibition potency of 81.6% and 83.4% at 20 μM, respectively. Additionally, molecular docking was performed to identify the possible factor responsible for the enantioselectivity in the anti-Aβ 1–42 aggregation activity.
      Graphical abstract image

      PubDate: 2018-06-06T13:56:11Z
      DOI: 10.1016/j.bioorg.2018.05.016
      Issue No: Vol. 80 (2018)
       
  • Nitric oxide inhibitory constituents from Siegesbeckia pubescens
    • Authors: Hari Jang; Jin Woo Lee; Jun Gu Kim; Hye Ryoung Hong; Thi Phoung Linh Le; Jin Tae Hong; Youngsoo Kim; Mi Kyeong Lee; Bang Yeon Hwang
      Pages: 81 - 85
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Hari Jang, Jin Woo Lee, Jun Gu Kim, Hye Ryoung Hong, Thi Phoung Linh Le, Jin Tae Hong, Youngsoo Kim, Mi Kyeong Lee, Bang Yeon Hwang
      Two new sesquiterpenoids (1 and 2) and a new ent-pimarane type diterpenoid (3), together with eighteen known compounds (4–21), were isolated from the whole plants of Siegesbeckia pubescens. The structures of the new compounds were determined on the basis of 1D-, 2D NMR and HRESIMS data. All compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Of these, highly oxygenated germacrane type sesquiterpenoids (1–2 and 13–14) showed significant inhibitory effects with IC50 values ranging from 3.9 to 16.8 μM.
      Graphical abstract image

      PubDate: 2018-06-09T13:58:16Z
      DOI: 10.1016/j.bioorg.2018.05.022
      Issue No: Vol. 80 (2018)
       
  • Multi-targetable chalcone analogs to treat deadly Alzheimer’s disease:
           Current view and upcoming advice
    • Authors: Xu Zhang; K.P. Rakesh; S.N.A. Bukhari; Moku Balakrishna; H.M. Manukumar; Hua-Li Qin
      Pages: 86 - 93
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Xu Zhang, K.P. Rakesh, S.N.A. Bukhari, Moku Balakrishna, H.M. Manukumar, Hua-Li Qin
      The complications of Alzheimer’s disease AD were deadly dangerous cause of neurodegenerative disorders connected with the decline of the cognitive functions and loss of memory. The common form of dementia is accounted as the sixth leading cause of the death affecting any stage of people in a lifetime. Synthetic natural chalcone analogs were currently a hot research topic for the treatment of (AD) which has affected millions of peoples throughout the world. The present aim was set to understand the important problems of the AD and its treatment based on natural derivatives of novel chalcones. One interesting strategy currently of searching for the treatment of AD is to find inhibitors for acetylcholinesterase (AChE) and using metal chelators to target amyloid-β (Aβ) peptides, and then metal-Aβ complexes for the AD pathogenesis. The present compressed review focuses and highlights the design and synthesis of new approaches for the construction of important chalcones playing multiple beneficiary roles in the AD treatments. These hallmarks of concurred research represent the immediate needs of development of novel therapeutic drugs for effective treatment of ADs by understanding the specific pharmacology targets.
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      PubDate: 2018-06-09T13:58:16Z
      DOI: 10.1016/j.bioorg.2018.06.009
      Issue No: Vol. 80 (2018)
       
  • Synthesis and molecular docking study of some novel 2,3-disubstituted
           quinazolin-4(3H)-one derivatives as potent inhibitors of urease
    • Authors: Gülay Akyüz; Emre Menteşe; Mustafa Emirik; Nimet Baltaş
      Pages: 121 - 128
      Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Gülay Akyüz, Emre Menteşe, Mustafa Emirik, Nimet Baltaş
      A new series of 2,3-disubstituted quinazolin-4(3H)-one compounds including oxadiazole and furan rings was synthesized. Their inhibitory activities on urease were assessed in vitro. All newly synthesized compounds exhibited potent urease inhibitory activity in the range of IC50 = 1.55 ± 0.07–2.65 ± 0.08 µg/mL, when compared with the standard urease inhibitors such as thiourea (IC50 = 15.08 ± 0.71 µg/mL) and acetohydroxamic acid (IC50 = 21.05 ± 0.96 µg/mL). 2,3-Disubstituted quinazolin-4(3H)-one derivatives containing furan ring (3a-e) were found to be the most active inhibitors when compared with the compounds 2a-e bearing oxadiazole ring. Compound 3a, bearing 4-chloro group on phenyl ring, was found as the most effective inhibitor of urease with the IC50 value of 1.55 ± 0.11 µg/mL. The molecular docking studies of the newly synthesized compounds were performed to identify the probable binding modes in the active site of the Jack bean urease (JBU) enzymes.
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      PubDate: 2018-06-09T13:58:16Z
      DOI: 10.1016/j.bioorg.2018.06.011
      Issue No: Vol. 80 (2018)
       
  • Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential
           anti-HIV-1 agents
    • Authors: Subhash Chander; Cheng-Run Tang; Ashok Penta; Ping Wang; Deepak P. Bhagwat; Nicolas Vanthuyne; Muriel Albalat; Payal Patel; Sanskruti Sankpal; Yong-Tang Zheng; Murugesan Sankaranarayanan
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Subhash Chander, Cheng-Run Tang, Ashok Penta, Ping Wang, Deepak P. Bhagwat, Nicolas Vanthuyne, Muriel Albalat, Payal Patel, Sanskruti Sankpal, Yong-Tang Zheng, Murugesan Sankaranarayanan
      In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1K103N strain. The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.027
      Issue No: Vol. 79 (2018)
       
  • Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents
           for potential treatment of Alzheimer's disease
    • Authors: Leili Jalili-Baleh; Hamid Nadri; Hamid Forootanfar; Alireza Samzadeh-Kermani; Tuba Tüylü Küçükkılınç; Beyza Ayazgok; Mahban Rahimifard; Maryam Baeeri; Mohsen Doostmohammadi; Loghman Firoozpour; Syed Nasir Abbas Bukhari; Mohammad Abdollahi; Mohammad Reza Ganjali; Saeed Emami; Mehdi Khoobi; Alireza Foroumadi
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Leili Jalili-Baleh, Hamid Nadri, Hamid Forootanfar, Alireza Samzadeh-Kermani, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Mahban Rahimifard, Maryam Baeeri, Mohsen Doostmohammadi, Loghman Firoozpour, Syed Nasir Abbas Bukhari, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
      New series of triazole-containing 3-phenylcoumarin–lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2O2-induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations. Based on the obtained results, the benzocoumarin derivative 4j with IC50 value of 7.3 µM was the most potent AChE inhibitor and displayed good inhibition toward intracellular reactive oxygen species (ROS). This compound with antioxidant and metal chelating ability showed also protective effect on cell injury induced by Aβ1-42 in SH-SY5Y cells. Although the 8-methoxycoumarin analog 4i was slightly less active than 4j against AChE, but displayed higher protection ability against H2O2-induced cell death in PC12 and could significantly block Aβ-aggregation. The results suggested that the prototype compounds 4i and 4j might be promising multi-functional agents for the further development of the disease-modifying treatments of Alzheimer's disease.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.030
      Issue No: Vol. 79 (2018)
       
  • Design and synthesis of some new carboxamide and propanamide derivatives
           bearing phenylpyridazine as a core ring and the investigation of their
           inhibitory potential on in-vitro acetylcholinesterase and
           butyrylcholinesterase
    • Authors: Burcu Kilic; Hayrettin O. Gulcan; Fatma Aksakal; Tugba Ercetin; Nihan Oruklu; E. Umit Bagriacik; Deniz S. Dogruer
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Burcu Kilic, Hayrettin O. Gulcan, Fatma Aksakal, Tugba Ercetin, Nihan Oruklu, E. Umit Bagriacik, Deniz S. Dogruer
      A series of new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring were designed, synthesized and evaluated for their ability to inhibit both cholinesterase enzymes. In addition, a series of carboxamide and propanamide derivatives bearing biphenyl instead of phenylpyridazine were also synthesized to examine the inhibitory effect of pyridazine moiety on both cholinesterase enzymes. The inhibitory activity results revealed that compounds 5b, 5f, 5h, 5j, 5l pyridazine-3-carboxamide derivative, exhibited selective acetylcholinesterase (AChE) inhibition with IC50 values ranging from 0.11 to 2.69 µM. Among them, compound 5h was the most active one (IC50 = 0.11 µM) without cytotoxic effect at its effective concentration against AChE. Additionally, pyridazine-3-carboxamide derivative 5d (IC50 for AChE = 0.16 µM and IC50 for BChE = 9.80 µM) and biphenyl-4-carboxamide derivative 6d (IC50 for AChE = 0.59 µM and IC50 for BChE = 1.48 µM) displayed dual cholinesterase inhibitory activity. Besides, active compounds were also tested for their ability to inhibit Aβ aggregation. Theoretical physicochemical properties of the compounds were calculated by using Molinspiration Program as well. The Lineweaver-Burk plot and docking study showed that compound 5 h targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.006
      Issue No: Vol. 79 (2018)
       
  • Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the
           fungus Drechmeria sp. as a natural agonist of human pregnane X receptor
    • Authors: Jian-Chao Zhao; Zhi-Lin Luan; Jia-Hao Liang; Zhong-Bin Cheng; Cheng-Peng Sun; Ya-Li Wang; Meng-Yue Zhang; Tian-Yuan Zhang; Yong Wang; Tian-Mei Yang; Ying-Ying Wu; Yi-Xuan Zhang; Xin-Yu Zhao; Xiao-Chi Ma
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Jian-Chao Zhao, Zhi-Lin Luan, Jia-Hao Liang, Zhong-Bin Cheng, Cheng-Peng Sun, Ya-Li Wang, Meng-Yue Zhang, Tian-Yuan Zhang, Yong Wang, Tian-Mei Yang, Ying-Ying Wu, Yi-Xuan Zhang, Xin-Yu Zhao, Xiao-Chi Ma
      A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H (1), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2′-epi terpendole A (3), and a known analogue, terpendole A (2). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A (2) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC50 value of 134.91 ± 2.01 nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1–3 is also discussed in the present work.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.001
      Issue No: Vol. 79 (2018)
       
  • Discovery of antitumor ursolic acid long-chain diamine derivatives as
           potent inhibitors of NF-κB
    • Authors: Wei Jiang; Ri-Zhen Huang; Jing Zhang; Tong Guo; Meng-Ting Zhang; Xiao-Chao Huang; Bin Zhang; Zhi-Xin Liao; Jing Sun; Heng-Shan Wang
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Wei Jiang, Ri-Zhen Huang, Jing Zhang, Tong Guo, Meng-Ting Zhang, Xiao-Chao Huang, Bin Zhang, Zhi-Xin Liao, Jing Sun, Heng-Shan Wang
      A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC50 values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 5.22 to 8.95 μM. Moreover, compound 8c successfully suppressed the migration of A549 cells. Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-κB signalling pathway. Molecular docking study revealed that key interactions between 8c and the active site of NF-κB in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.005
      Issue No: Vol. 79 (2018)
       
  • Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom
           tyrosinase enzyme inhibition assay and in silico comparative molecular
           docking analysis with Kojic acid
    • Authors: Pervaiz Ali Channar; Aamer Saeed; Fayaz Ali Larik; Bakhtawar Batool; Saima Kalsoom; M.M. Hasan; Mauricio F. Erben; Hesham R. El-Seedi; Musrat Ali; Zaman Ashraf
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Pervaiz Ali Channar, Aamer Saeed, Fayaz Ali Larik, Bakhtawar Batool, Saima Kalsoom, M.M Hasan, Mauricio F. Erben, Hesham R. El-Seedi, Musrat Ali, Zaman Ashraf
      Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (−6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.026
      Issue No: Vol. 79 (2018)
       
  • Design, synthesis, biological evaluation, structure-activity relationship
           study, and mode of action of 2-phenol-4,6-dichlorophenyl-pyridines
    • Authors: Aarajana Shrestha; Seojeong Park; Somin Shin; Tara Man Kadayat; Ganesh Bist; Pramila Katila; Youngjoo Kwon; Eung-Seok Lee
      Pages: 1 - 18
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Aarajana Shrestha, Seojeong Park, Somin Shin, Tara Man Kadayat, Ganesh Bist, Pramila Katila, Youngjoo Kwon, Eung-Seok Lee
      Human DNA topoisomerases (Topos) are essential nuclear enzyme whose level of expression is potential indicator for prediction of responsive result of chemotherapy. Topos has become a key cellular target for most of the anticancer agents that regulates topological problems of DNA during cellular metabolic processes such as replication, transcription, and recombination. Inspired by previous studies of 2,4,6-trisubstituted pyridines to find out safer and effective topoisomerase targeted anticancer agent, twenty-seven 2-phenol-4,6-dichlorophenyl-pyridines were designed, synthesized, and tested for their topo I and IIα inhibitory and anti-proliferative activity. Most of the dichlorinated meta- and para-phenolic series compounds (1–18) exhibited potent and selective topo IIα inhibition along with significant anti-proliferative activity in the HCT-15 and T47D cell lines compared to the positive control, etoposide. Interestingly, dichlorinated ortho-phenolic series compounds (19–27) exhibited potent and dual topo inhibition but very weak anti-proliferative activity in the tested cancer cell lines. Structure-activity relationship with previously synthesized compounds revealed the importance of chlorine moiety to improve the potency of topo inhibitory activity. Further mechanistic study confirmed that compounds 2 and 12 acted as non-intercalative specific topo IIα catalytic inhibitor with less DNA damage, and induced G1 arrest and apoptosis in HCT-15 and T47D cell lines, respectively.
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      PubDate: 2018-05-02T03:42:02Z
      DOI: 10.1016/j.bioorg.2018.03.033
      Issue No: Vol. 79 (2018)
       
  • New α-Glucosidase inhibitors from the resins of Boswellia species with
           structure–glucosidase activity and molecular docking studies
    • Authors: Najeeb Ur. Rehman; Ajmal Khan; Ahmed Al-Harrasi; Hidayat Hussain; Abdul Wadood; Muhammad Riaz; Zahra Al-Abri
      Pages: 27 - 33
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Najeeb Ur. Rehman, Ajmal Khan, Ahmed Al-Harrasi, Hidayat Hussain, Abdul Wadood, Muhammad Riaz, Zahra Al-Abri
      Phytochemical investigation of the oleo-gum resins from Boswellia papyrifera afforded one new triterpene, named 3α-hydroxyurs-5:19-diene (1) together with twelve known compounds including eight triterpenoids (2–9), two diterpenoids (10 and 11) and two straight chain alkanes (12 and 13). Similarly ten more known compounds were isolated from the resin of Boswellia sacra including one triterpene (20) and nine boswellic acids (14–19 and 21–23). Herein the compound 2 was first time reporting from natural source along with complete NMR assignment, while compounds 3–11 are known, but reported for the first time from the resin of B. papyrifera. The structure elucidation was done by advance spectroscopic 1D and 2D NMR techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. All compounds were evaluated for their α-glucosidase inhibitory activity and as result eight of them 1, 3, 10, 11, 15, and 17–19 were found significantly active against α-glucosidase with an IC50 value ranging from 15.0 ± 0.84 to 80.3 ± 2.33 µM, while 21 exhibited moderate activity with IC50 of 799.9 ± 4.98 µM. Furthermore, two compounds 24 and 25 were synthesised from 16 and 17 to see the effect of carboxyl group in structural-activity relationship (SAR) study. Compounds 24 and 25 retained good α-glucosidase inhibition as compared to 16 and 17, indicating that carboxylic group play a key role in SAR. In addition, the aforementioned activity of all the active compounds was first time reported for their α-glucosidase inhibition potential. The molecular docking studies showed that all the active compounds well accommodate in the active site of the enzyme. Moreover pharmacokinetic properties of the compounds were predicted in silico, suggesting that the compounds possess drug like properties and excellent ADMET profile.
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      PubDate: 2018-05-02T03:42:02Z
      DOI: 10.1016/j.bioorg.2018.04.020
      Issue No: Vol. 79 (2018)
       
  • Synthetic nicotinic/isonicotinic thiosemicarbazides: In vitro urease
           inhibitory activities and molecular docking studies
    • Authors: Basharat Ali; Khalid Mohammed Khan; Arshia; Kanwal; Shafqat Hussain; Safdar Hussain; Muhammad Ashraf; Muhammad Riaz; Abdul Wadood; Shahnaz Perveen
      Pages: 34 - 45
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Basharat Ali, Khalid Mohammed Khan, Arshia, Kanwal, Shafqat Hussain, Safdar Hussain, Muhammad Ashraf, Muhammad Riaz, Abdul Wadood, Shahnaz Perveen
      Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3–27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1H-, and 13C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC50 values of 1.21–51.42 μM as compared to the standard thiourea (IC50 = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1–5, 7, 8, 10, 12, 14–18, 20–22, 24–27 were found to be more active showing IC50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study.
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      PubDate: 2018-05-02T03:42:02Z
      DOI: 10.1016/j.bioorg.2018.04.004
      Issue No: Vol. 79 (2018)
       
  • Synthesis, anticancer evaluation, and molecular docking studies of some
           novel 4,6-disubstituted pyrazolo[3,4-d]pyrimidines as cyclin-dependent
           kinase 2 (CDK2) inhibitors
    • Authors: Srinivasulu Cherukupalli; Balakumar Chandrasekaran; Vladimír Kryštof; Rajeshwar Reddy Aleti; Nisar Sayyad; Srinivas Reddy Merugu; Narva Deshwar Kushwaha; Rajshekhar Karpoormath
      Pages: 46 - 59
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Srinivasulu Cherukupalli, Balakumar Chandrasekaran, Vladimír Kryštof, Rajeshwar Reddy Aleti, Nisar Sayyad, Srinivas Reddy Merugu, Narva Deshwar Kushwaha, Rajshekhar Karpoormath
      A novel series of 4,6-disubstituted pyrazolo[3,4-d]pyrimidines (7–43) bearing various anilines at C-4 position and thiophenethyl or thiopentane moieties at C-6 position have been designed and synthesized by molecular hybridization approach. All the synthesized compounds were evaluated for in vitro CDK2/cyclin E and Abl kinase inhibitory activity as well as anti-proliferative activity against K-562 (chronic myelogeneous leukemia), and MCF-7 (breast adenocarcinoma) cell lines. The structure–activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. The in silico molecular docking studies suggested possible binding orientation and the binding energies were in agreement with the observed SAR as well as experimental results. In addition, some of the synthesized compounds showed anti-proliferative effects against K-562 and MCF-7 cancer cell lines with IC50 values in a micromolar range. Thus, the synthesized compounds could be considered as new anticancer hits for further lead optimization.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.02.030
      Issue No: Vol. 79 (2018)
       
  • New AChE inhibitors from microbial transformation of trachyloban-19-oic
           acid by Syncephalastrum racemosum
    • Authors: Gabriel Franco dos Santos; Gesiane da Silva Lima; Geane Pereira de Oliveira; José Dias de Souza Filho; Luciana da Silva Amaral; Edson Rodrigues-Filho; Jacqueline Aparecida Takahashi
      Pages: 60 - 63
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Gabriel Franco dos Santos, Gesiane da Silva Lima, Geane Pereira de Oliveira, José Dias de Souza Filho, Luciana da Silva Amaral, Edson Rodrigues-Filho, Jacqueline Aparecida Takahashi
      Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2–3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1–4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimer’s disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50 = 0.06 μM, which is about six times higher than activity found for galanthamine (IC50 = 0.38 μM), the positive control used in this assay.
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      PubDate: 2018-05-02T03:42:02Z
      DOI: 10.1016/j.bioorg.2018.04.011
      Issue No: Vol. 79 (2018)
       
  • Steroids from Ganoderma sinense as new natural inhibitors of
           cancer-associated mutant IDH1
    • Authors: Mengzhu Zheng; Ruotian Tang; Yue Deng; Kaiyin Yang; Lixia Chen; Hua Li
      Pages: 89 - 97
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Mengzhu Zheng, Ruotian Tang, Yue Deng, Kaiyin Yang, Lixia Chen, Hua Li
      Isocitrate dehydrogenase (IDH) is one of the key enzymes in the tricarboxylic acid cycle, and IDH mutations have been associated with many cancers, including glioblastoma, sarcoma, acute myeloid leukemia, etc. Three natural steroids 1–3 from Ganoderma sinense, a unique and rare edible-medicinal fungi in China, were found as potential IDH1 inhibitors by virtual ligand screening method. Among the three compounds, 3 showed the highest binding affinity to IDH1 with significant calculated binding free energy. Enzymatic kinetics demonstrated that 3 inhibited mutant enzyme in a noncompetitive manner. The half effective concentration of 3 for reducing the concentration of D-2HG in HT1080 cells was 35.97 μM. The levels of histone H3K9me3 methylation in HT1080 cells were reduced by treating with 3. Furthermore, knockdown of mutant IDH1 in HT1080 cells decreased the anti-proliferative sensitivity to 3. In short, our findings highlight that compound 3 may have clinical potential in tumor therapies as an effective inhibitor of mutant IDH1.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.016
      Issue No: Vol. 79 (2018)
       
  • Functional group and stereochemical requirements for substrate binding by
           ghrelin O-acyltransferase revealed by unnatural amino acid incorporation
    • Authors: Elizabeth R. Cleverdon; Tasha R. Davis; James L. Hougland
      Pages: 98 - 106
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Elizabeth R. Cleverdon, Tasha R. Davis, James L. Hougland
      Ghrelin is a small peptide hormone that undergoes a unique posttranslational modification, serine octanoylation, to play its physiological roles in processes including hunger signaling and glucose metabolism. Ghrelin O-acyltransferase (GOAT) catalyzes this posttranslational modification, which is essential for ghrelin to bind and activate its cognate GHS-R1a receptor. Inhibition of GOAT offers a potential avenue for modulating ghrelin signaling for therapeutic effect. Defining the molecular characteristics of ghrelin that lead to binding and recognition by GOAT will facilitate the development and optimization of GOAT inhibitors. We show that small peptide mimics of ghrelin substituted with 2,3-diaminopropanoic acid in place of the serine at the site of octanoylation act as submicromolar inhibitors of GOAT. Using these chemically modified analogs of desacyl ghrelin, we define key functional groups within the N-terminal sequence of ghrelin essential for binding to GOAT and determine GOAT’s tolerance to backbone methylations and altered amino acid stereochemistry within ghrelin. Our study provides a structure-activity analysis of ghrelin binding to GOAT that expands upon activity-based investigations of ghrelin recognition and establishes a new class of potent substrate-mimetic GOAT inhibitors for further investigation and therapeutic interventions targeting ghrelin signaling.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.009
      Issue No: Vol. 79 (2018)
       
  • Novel tetrahydrofuran derivatives from Trigonostemon howii with their
           potential anti-HIV-1 activities
    • Authors: Yan-Ping Liu; Wan-Hui Zhao; Xing-Yang Feng; Zhi-Jie Zhang; Kang Zong; Zhi-Guo Sun; Yong-Tang Zheng; Yan-Hui Fu
      Pages: 111 - 114
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Yan-Ping Liu, Wan-Hui Zhao, Xing-Yang Feng, Zhi-Jie Zhang, Kang Zong, Zhi-Guo Sun, Yong-Tang Zheng, Yan-Hui Fu
      A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives (2–6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetrahydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbon skeleton and the known compouds (2–6) are rare tetrahydrofuran derivatives in the plant kingdom with various carbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1–6 showed significant anti-HIV-1 activities with EC50 ranged from 0.08 to 1.03 µM. These findings suggest that the discoveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could be of great importance to the development of new anti-HIV agents.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.023
      Issue No: Vol. 79 (2018)
       
  • A novel derivatives of thiazol-4(5H)-one and their activity in the
           inhibition of 11β-hydroxysteroid dehydrogenase type 1
    • Authors: Renata Studzińska; Renata Kołodziejska; Daria Kupczyk; Wojciech Płaziński; Tomasz Kosmalski
      Pages: 115 - 121
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Renata Studzińska, Renata Kołodziejska, Daria Kupczyk, Wojciech Płaziński, Tomasz Kosmalski
      11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes the conversion of inactive cortisone into physiologically active cortisol. Inhibiting the activity of this enzyme plays a key role in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. Therefore, new compounds that are selective inhibitors of this enzyme are constantly being looked for. In this work we present the synthesis of 2-(allylamino)thiazol-4(5H)-one derivatives by the reaction of N-allylthiourea with appropriate α-bromoesters. In the case of using of aliphatic α-bromoesters and α-bromo-β-phenylesters, the reactions were carried out in a basic medium (sodium ethoxide) and the products were isolated with a yield of up to 68%. Derivatives containing spiro systems in which carbon C-5 of the thiazole ring is the linker atom were obtained in the presence of N,N-diisopropylethylamine. Some of the obtained compounds, at a concentration of 10 μM have activity in the inhibition of 11β-HSD1 up to 71%. IC50 value for the most active compound: 2-(allylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one is 2.5 µM. With a high degree of 11β-HSD1 inhibition and a relatively large difference in the inhibition of 11β-HSD1 and 11β-HSD2 activity, this compound appears to be promising and should be subjected to further testing.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.014
      Issue No: Vol. 79 (2018)
       
  • Supramolecular nanofiber of pyrene-lactose conjugates and its two-photon
           fluorescence imaging
    • Authors: Qian Sun; Hong-Yu Zhu; Jun-Fang Wang; Xiao Chen; Ke-Rang Wang; Xiao-Liu Li
      Pages: 126 - 130
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Qian Sun, Hong-Yu Zhu, Jun-Fang Wang, Xiao Chen, Ke-Rang Wang, Xiao-Liu Li
      A lactose modified pyrene derivative (Py-Lac) was synthesized, with which novel twisted supramolecular nanofibers in diameter about 20 nm were constructed by self-assembly. The nanofibers showed solid-state fluorescence between 400 nm and 650 nm with the maximum emission at 495 nm. Furthermore, its recognition reaction with PNA lectin was investigated by fluorescence spectra and turbidity assays. It is interesting found that the supramolecular assembly as multivalent glycocluster exhibited unique and selectively binding interactions with PNA lectin with the binding constant of 5.74 × 106 M−1. Moreover, compound Py-Lac showed two-photon fluorescence imaging with Hep G2 cells.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.013
      Issue No: Vol. 79 (2018)
       
  • Molecular modelling and synthesis of spiroimidazolidine-2,4-diones with
           dual activities as hypoglycemic agents and selective inhibitors of aldose
           reductase
    • Authors: Manar G. Salem; Yasmine M. Abdel Aziz; Marwa Elewa; Hosam A. Elshihawy; Mohamed M. Said
      Pages: 131 - 144
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Manar G. Salem, Yasmine M. Abdel Aziz, Marwa Elewa, Hosam A. Elshihawy, Mohamed M. Said
      Novel derivatives of spiroimidazolidinedione were synthesized and evaluated as hypoglycemic agents through binding to sulfonylurea receptor 1 (SUR1) in pancreatic beta-cells. Their selectivity index was calculated against both aldehyde reductase (ALR1) and aldose reductase (ALR2). Aldehyde reductase is a key enzyme in the polyol pathway that is involved in the etiology of the secondary diabetic complications. All structures were confirmed by microanalysis and by IR, 1H NMR, 13C NMR and EI-MS spectroscopy. The investigated compounds were subjected to molecular docking and an in silico prediction study to determine their free energy of binding (ΔG) values and predict their physicochemical properties and drug-likeness scores. Compound 1′-(5-chlorothiophene-2-ylsulfonyl)spiro[cyclohexane-1,5′-imidazolidine]-2′,4′-dione showed IC50 0.47 µM and 79% reduction in blood glucose level with a selectivity index 127 for ALR2.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.028
      Issue No: Vol. 79 (2018)
       
  • Structure-activity relationships of rationally designed AMACR 1A
           inhibitors
    • Authors: Maksims Yevglevskis; Guat L. Lee; Amit Nathubhai; Yoana D. Petrova; Tony D. James; Michael D. Threadgill; Timothy J. Woodman; Matthew D. Lloyd
      Pages: 145 - 154
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Maksims Yevglevskis, Guat L. Lee, Amit Nathubhai, Yoana D. Petrova, Tony D. James, Michael D. Threadgill, Timothy J. Woodman, Matthew D. Lloyd
      α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the ‘racemisation’ reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure–activity relationship study has been performed. This paper describes the first structure–activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC50 = 400–750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure–activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.024
      Issue No: Vol. 79 (2018)
       
  • Synthesis, biological evaluation and molecular modeling of
           2-amino-2-phenylethanol derivatives as novel β2-adrenoceptor agonists
    • Authors: Xinyue Ge; Yongmei Mo; Gang Xing; Lei Ji; Haiyan Zhao; Jianfang Chen; Bin He; Xuyao Chen; Ruijuan Xing; Xiaoqiang Li; Ying Zhao; Jinyan Li; Haining Yan; Anthony Yiu-Ho Woo; Yuyang Zhang; Bin Lin; Li Pan; Maosheng Cheng
      Pages: 155 - 162
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Xinyue Ge, Yongmei Mo, Gang Xing, Lei Ji, Haiyan Zhao, Jianfang Chen, Bin He, Xuyao Chen, Ruijuan Xing, Xiaoqiang Li, Ying Zhao, Jinyan Li, Haining Yan, Anthony Yiu-Ho Woo, Yuyang Zhang, Bin Lin, Li Pan, Maosheng Cheng
      A novel series of 2-amino-2-phenylethanol derivatives were developed as β2-adrenoceptor agonists. Among them, 2-amino-3-fluoro-5-(2-hydroxy-1-(isopropylamino)ethyl)benzonitrile (compound 2f) exhibited the highest activity (EC50 = 0.25 nM) in stimulating β2-adrenoceptor-mediated cellular cAMP production with a 763.6-fold selectivity over the β1-adrenoceptor. The (S)-isomer of 2f was subsequently found to be 8.5-fold more active than the (R)-isomer. Molecular docking was performed to determine the putative binding modes of this new class of β2-adrenoceptor agonists. Taken together, these data show that compound 2f is a promising lead compound worthy of further study for the development of β2-adrenoceptor agonists.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.017
      Issue No: Vol. 79 (2018)
       
  • Synthesis and molecular docking of N,N′-disubstituted thiourea
           derivatives as novel aromatase inhibitors
    • Authors: Ratchanok Pingaew; Veda Prachayasittikul; Nuttapat Anuwongcharoen; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul
      Pages: 171 - 178
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Ratchanok Pingaew, Veda Prachayasittikul, Nuttapat Anuwongcharoen, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul
      A three series of thioureas, monothiourea type I (4a–g), 1,4-bisthiourea type II (5a–h) and 1,3-bisthiourea type III (6a–h) were synthesized. Their aromatase inhibitory activities have been evaluated. Interestingly, eight thiourea derivatives (4e, 5f–h, 6d, 6f–h) exhibited the aromatase inhibitory activities with IC50 range of 0.6–10.2 μM. The meta-bisthiourea bearing 4-NO2 group (6f) and 3,5-diCF3 groups (6h) were shown to be the most potent compounds with sub-micromolar IC50 values of 0.8 and 0.6 μM, respectively. Molecular docking also revealed that one of the thiourea moieties of these two compounds could mimic steroidal backbone of the natural androstenedione (ASD) via hydrophobic interactions with enzyme residues (Val370, Leu477, Thr310, and Phe221 for 6f, Val370, Leu477, Ser478, and Ile133 for 6h). This is the first time that the bisthioureas have been reported for their potential to be developed as aromatase inhibitors, in which the 4-NO2 and 3,5-diCF3 analogs have been highlighted as promising candidates.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.002
      Issue No: Vol. 79 (2018)
       
  • Chalcones and bis-chalcones: As potential α-amylase inhibitors;
           synthesis, in vitro screening, and molecular modelling studies
    • Authors: Adebayo Tajudeen Bale; Khalid Mohammed Khan; Uzma Salar; Sridevi Chigurupati; Tolulope Fasina; Farman Ali; Kanwal; Abdul Wadood; Muhammad Taha; Sitanshu Sekhar Nanda; Mehreen Ghufran; Shahnaz Perveen
      Pages: 179 - 189
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Adebayo Tajudeen Bale, Khalid Mohammed Khan, Uzma Salar, Sridevi Chigurupati, Tolulope Fasina, Farman Ali, Kanwal, Abdul Wadood, Muhammad Taha, Sitanshu Sekhar Nanda, Mehreen Ghufran, Shahnaz Perveen
      Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1–13 and bis-chalcones 14–18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05–2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure–activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.003
      Issue No: Vol. 79 (2018)
       
  • Synthesis of steroidal imidazolidinthiones as potential apoptotic agents:
           Investigation by theoretical and experimental studies
    • Authors: Ayaz Mahmood Dar; Rizwan Nabi; Shafia Mir; Manzoor Ahmad Gatoo; Shamsuzzaman; Shabir H. Lone
      Pages: 190 - 200
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Ayaz Mahmood Dar, Rizwan Nabi, Shafia Mir, Manzoor Ahmad Gatoo, Shamsuzzaman, Shabir H. Lone
      New steroidal imidazolidinthione derivatives (4–6) were synthesized from steroidal thiosemicarbazones and dichloroethane. The synthesized compounds were characterized using spectral data analysis. Theoretical DFT involving B3LYP/6-31G∗∗ level of theory was employed to gain insights into the molecular structure of the target compounds. MEPS and FMO analysis were carried out. HOMO-LUMO energy gap was determined which helped to evaluate various global descriptors like hardness, chemical potential, electronegativity, nucleophilicity and electrophilicity index, etc. The calculated properties established that the synthesized products are more or less similar in their reactivity behaviour. To explore their biological potential, interaction studies of compounds (4–6) with DNA were carried out using various biophysical techniques. The compounds bind DNA preferentially through electrostatic and hydrophobic interactions with Kb of 3.21 × 103 M−1, 2.79 × 103 M−1 and 2.26 × 103 M−1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis of compound 4 demonstrated strong interaction during the concentration dependent cleavage activity with pBR322 DNA. It was observed that these steroidal imidazolidinthiones are minor groove binders of DNA which was validated using molecular docking studies. An in vitro cytotoxicity screening using MTT assay revealed that the compounds (4–6) exhibit potential toxicity against different human cancer cells. Highest antiproliferative effect was observed on HeLa cells by compound 4. The results suggested that compounds 4–6 cause apoptotic cell death by cleaving apoptotic protein caspase-3 and suppress anti-apoptotic protein Bcl-2 in HeLa cancer cells.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.029
      Issue No: Vol. 79 (2018)
       
  • Synthesis, molecular docking and xanthine oxidase inhibitory activity of
           5-aryl-1H-tetrazoles
    • Authors: Itrat Fatima; Humaira Zafar; Khalid Mohammed Khan; Syed Muhammad Saad; Sumaira Javaid; Shahnaz Perveen; M. Iqbal Choudhary
      Pages: 201 - 211
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Itrat Fatima, Humaira Zafar, Khalid Mohammed Khan, Syed Muhammad Saad, Sumaira Javaid, Shahnaz Perveen, M. Iqbal Choudhary
      5-Aryl-1H-tetrazoles (1–24) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC50 = 2.0 ± 0.01 µM). Six compounds 3, 4, 5, 9, 21, and 24 exhibited significant to weak activities with IC50 values in the range of 7.4–174.2 µM. Active compounds were further subjected to kinetic and molecular docking studies to deduce their modes of inhibition, and to study their interactions with the protein (XO) at atomic level, respectively. Interestingly, all these compounds showed a competitive mode of inhibition. Docking studies identified several important interactions between the ligand and the receptor protein (XO). Some of these interactions were similar to that exhibited by clinical inhibitors of XO (allopurinol, and febuxostat). This study identifies 5-aryl-1H-tetrazoles as a new class of xanthine oxidase inhibitors, which deserves to be further, investigated for the treatment of hyperuricemia and gout.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.021
      Issue No: Vol. 79 (2018)
       
  • Discovery of potent α-glucosidase inhibitor flavonols: Insights into
           mechanism of action through inhibition kinetics and docking simulations
    • Authors: Didem Şöhretoğlu; Suat Sari; Burak Barut; Arzu Özel
      Pages: 257 - 264
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Didem Şöhretoğlu, Suat Sari, Burak Barut, Arzu Özel
      Beside other pharmaceutical benefits, flavonoids are known for their potent α-glucosidase inhibition. In the present study, we investigated α-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3″-O-galloyl)-β-galactopyranoside (8) and quercetin 3-O-(6″-O-galloyl)-β-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC50 values of 0.97 ± 0.02 and 1.35 ± 0.06 µM, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the α-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.05.010
      Issue No: Vol. 79 (2018)
       
  • Leveraging the cruzain S3 subsite to increase affinity for reversible
           covalent inhibitors
    • Authors: Lorenzo Cianni; Geraldo Sartori; Fabiana Rosini; Daniela De Vita; Gabriel Pires; Bianca Rebelo Lopes; Andrei Leitão; Antonio C.B. Burtoloso; Carlos A. Montanari
      Pages: 285 - 292
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Lorenzo Cianni, Geraldo Sartori, Fabiana Rosini, Daniela De Vita, Gabriel Pires, Bianca Rebelo Lopes, Andrei Leitão, Antonio C.B. Burtoloso, Carlos A. Montanari
      Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiological agent of Chagas disease. Reversible covalent cruzain inhibitors can block the steps of cell differentiation in the parasite and kill the organism. To this end, the description of how inhibitors modified at the P2/P3 positions lead to analogs with greater cruzain affinity to the S2/S3 subsites is of fundamental importance. Albeit many efforts are being employed in the characterization of the interaction processes with S2 subsite, little is known about the cruzain S3 subsite. In this work, we show a brief but consistent study to identify favorable substitutions in P3 of dipeptidyl nitriles that increase cruzain affinity. Using molecular dynamics simulations, we have identified some dipeptidyl nitrile analogs with modifications at P3 position that had higher cruzain inhibition than the original unsubstituted compound. A matched molecular pair analysis shows the importance of including a chlorine atom in the P3-meta position. The modifications implemented in P3 are confirmed when profiling the thermodynamic parameters via isothermal titration calorimetry. The classical enthalpy-entropy compensation phenomenon, in which enthalpy changes are counterbalanced by entropy results in a small modification of ΔG. The inclusion of the chlorine atom in the P3-meta position results in the highest reduction of the detrimental entropic contribution observed in P3.
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      PubDate: 2018-05-28T13:41:26Z
      DOI: 10.1016/j.bioorg.2018.04.006
      Issue No: Vol. 79 (2018)
       
  • The first activation studies of the η-carbonic anhydrase from the malaria
           parasite Plasmodium falciparum with amines and amino acids
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Andrea Angeli, Sonia Del Prete, Fatmah A.S. Alasmary, Linah S. Alqahtani, Zeid AlOthman, William A. Donald, Clemente Capasso, Claudiu T. Supuran
      The first activation study of a η-class carbonic anhydrase (CAs, EC 4.2.1.1) is reported. A panel of 24 natural and non-natural amino acids and amines was used to explore the activation profile of Plasmodium falciparum CA (PfACA). The most effective activators belonged to the amino acid chemotype, with d-Glu, l-Asp, l-/d-Phe and l-/d-DOPA possessing activation constant in the range of 82 nM–0.75 µM, whereas l-/d-His, l-Tyr, 4-amino-l-Phe and l-Gln were slightly less effective (KA in the range of 1.00–2.51 µM. The only amine with submicromolar activating properties was 1-(2-aminoethyl-piperazine) with a KA of 0.71 µM, whereas histamine, dopamine and serotonin showed KA ranging between 7.18 and 9.97 µM. As CA activators have scarcely been investigated for their interaction with protozoan CAs, this study may be relevant for an improved understanding of the role of this enzyme in the life cycle of the malaria producing organisms belonging to the genus Plasmodium.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo
           antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines
           
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Fatima Iftikhar, Farhana Yaqoob, Nida Tabassum, Muhammad Saeed Jan, Abdul Sadiq, Saba Tahir, Tahira Batool, Basit Niaz, Farzana Latif Ansari, Muhammad Iqbal Choudhary, Umer Rashid
      Thymidine phosphorylase (TP) is an angiogenic enzyme. It plays an important role in angiogenesis, tumour growth, invasion and metastasis. In current research work, we study the effect of structural modification of dihydropyrimidine-2-ones (DHPM-2-ones) on TP inhibition. A series of eighteen new derivatives of 3,4-dihydropyrimidone-2-one were designed and synthesized through the structural modification at C-6 position. All these new derivatives were then assessed for in-vitro inhibition of thymidine phosphorylase (TP) from E. coli. Oxadiazole derivatives 4a-e exhibited excellent TP-inhibition at low micromolar concentration levels better than standard drug 7-deazaxanthine (7-DX). Among all these compounds, 4b was found to be the most potent with IC50 = 1.09 ± 0.004 μM. Anti-angiogenesis potential of representative compounds were also studied in a chorioallantoic membrane (CAM) assay. Here again, compound 4b was found to be the potent anti-angiogenesis compound in a CAM assay. Docking studies were also performed with Molecular Operating Environment (MOE) to further analyse the mode of inhibition of these compounds. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme though stable hydrogen bonding and hydrophobic interactions.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Synthesis of Bis-indolylmethane sulfonohydrazides derivatives as potent
           α-Glucosidase inhibitors
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Mohammed Gollapalli, Muhammad Taha, Hayat Ullah, Muhammad Nawaz, Laode Muhammad Ramadhan AlMuqarrabun, Fazal Rahim, Faiza Qureshi, Ashik Mosaddik, Norizan Ahmat, Khalid Mohammed Khan
      In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Synthesis, in vitro urease inhibitory activity, and molecular docking
           studies of thiourea and urea derivatives
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Bilquees Bano, Kanwal, Khalid Mohammed Khan, Arif Lodhi, Uzma Salar, Farida Begum, Muhammad Ali, Muhammad Taha, Shahnaz Perveen
      The current study deals with the synthesis of urea and thiourea derivatives 1–37 which were characterized by various spectroscopic techniques including FAB-MS, 1H-, and 13C NMR. The synthetic compounds were subjected to urease inhibitory activity and compounds exhibited good to moderate urease inhibitory activity having IC50 values in range of 10.11–69.80 µM. Compound 1 (IC50 = 10.11 ± 0.11 µM) was found to be most active and even better as compared to the standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). A limited structure–activity relationship (SAR) was established and the compounds were also subjected to docking studies to confirm the binding interactions of ligands (compounds) with the active site of enzyme.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline
           scaffold as anti-proliferative tubulin polymerization inhibitors
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Mahmoud S. Abdelbaset, Gamal El-Din A. Abuo-Rahma, Mostafa H. Abdelrahman, Mohamed Ramadan, Bahaa G.M. Youssif, Syed Nasir Abbas Bukhari, Mamdouh F.A. Mohamed, Mohamed Abdel-Aziz
      A novel quinolinyl pyrrolone and quinolinyl pyridazinone derivatives has been synthesized and characterized using different spectroscopic and elemental analysis techniques. Most of the target compounds displayed promising antiproliferative activity; In general, the pyrrolone derivatives 4a-f exhibited higher antiproliferative activity than their corresponding pyridazinone. The pyrrolone 4f showed outstanding antiproliferative activity with moderate selectivity against CNS and renal cancer with selectivity ratio of 3.49 and 3.56, respectively. Compound 4e and 5d experienced tubulin polymerization inhibitory activity comparable to that of vincristine while 4c, 4e and 4d showed good BRAF kinase inhibition compared to Erlotinib. Docking of compound 4e into colchicine binding site and biological assay results revealed that these compounds act mainly through tubulin polymerization inhibitory mechanism and can exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Design, synthesis and evaluation of some pyrazolo[3,4-d]pyrimidine
           derivatives bearing thiazolidinone moiety as anti-inflammatory agents
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Rasha A. Nassra, Ibrahim M. Labouta
      Two new series of pyrazolo[3,4-d]pyrimidine bearing thiazolidinone moiety were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro (COX-1 and COX-2) inhibitory assay. Compounds that showed promising COX-2 selectivity were further subjected to in vivo anti-inflammatory screening applying formalin induced paw edema (acute model) and cotton-pellet induced granuloma (chronic model) assays using celecoxib and diclofenac sodium as reference drugs. The histopathological and ulcerogenic potential were also determined. In vivo anti-inflammatory data showed that compounds 2, 6, 7d displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, compounds 2, 3d, 3e, 7b and 7d displayed anti-inflammatory activity greater than or nearly equivalent to diclofenac sodium in the cotton pellet-induced granuloma assay. Moreover, most of the tested compounds revealed good gastrointestinal safety profile. Collectively, compounds 2 and 7d were considered as promising candidates in managing both acute and chronic inflammation with safe gastrointestinal margin.
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      PubDate: 2018-06-18T14:19:35Z
       
  • Efficient chemoenzymatic synthesis of (S)-α-amino-4-fluorobenzeneacetic
           acid using immobilized penicillin amidase
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Chao-Ping Lin, Xiao-Ling Tang, Ren-Chao Zheng, Yu-Guo Zheng
      An efficient chemoenzymatic route was developed for synthesis of (S)-α-amino-4-fluorobenzeneacetic acid, a valuable chiral intermediate of Aprepitant, using immobilized penicillin amidase catalyzed kinetic resolution of racemic N-phenylacetyl-4-fluorophenylglycine. The optimum temperature, pH and agitation rate of the reaction were determined to be 40 °C, 9.5 and 300 rpm, respectively. Kinetic resolution of 80 g L−1 N-phenylacetyl-4-fluorophenylglycine by immobilized amidase 20 g L−1 resulted in 49.9% conversion and >99.9% e.e. within 3 h. The unreacted N-phenylacetyl-4-fluorophenylglycine can be easily racemized and then recycled as substrate. The production of (S)-α-amino-4-fluorobenzeneacetic acid was further amplified in 1 L reaction system, affording excellent conversion (49.9%) and enantioselectivity (99.9%). This chemoenzymatic approach was demonstrated to be promising for industrial production of (S)-α-amino-4-fluorobenzeneacetic acid.
      Graphical abstract image

      PubDate: 2018-06-18T14:19:35Z
       
  • Synthesis and cholinesterase inhibitory activity of new 2-benzofuran
           carboxamide-benzylpyridinum salts
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Fahimeh Abedinifar, S. Morteza F. Farnia, Mohammad Mahdavi, Hamid Nadri, Alireza Moradi, Jahan B. Ghasemi, Tuba Tüylü Küçükkılınç, Loghman Firoozpour, Alireza Foroumadi
      A series of benzofuran-2-carboxamide-N-benzyl pyridinium halide derivatives (6a-o) are synthesized as new cholinesterase inhibitors. The synthetic pathway involves the reaction of salicylaldehyde derivatives and ethyl bromoacetate, followed by hydrolysis and amidation with 3- and 4-picolyl amine. Subsequently, N-((pyridin-4-yl) methyl) benzofuran-2-carboxamide and substituted N-((pyridin-3-yl) methyl) benzofuran-2-carboxamides reacts with benzyl halides to afford target compounds (6a-o). The chemical structures of all derivatives were confirmed by spectroscopic methods. The studies reveal that some of the synthesized compounds are potent butyrylcholinesterase inhibitors with IC50 values in the range of 0.054–2.7 µM. In addition, good inhibitory effects on Aβ self-aggregation are observed for 6h and 6k (33.1 and 46.4% at 100 µM, respectively).
      Graphical abstract image

      PubDate: 2018-06-18T14:19:35Z
       
  • Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl)
           phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors
           designed through bioisosteric modulation
    • Abstract: Publication date: October 2018
      Source:Bioorganic Chemistry, Volume 80
      Author(s): Neelesh Maheshwari, Chandrabose Karthikeyan, Shraddha V. Bhadada, Chandan Sahi, Amit K. Verma, N.S. Hari Narayana Moorthy, Piyush Trivedi
      Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes.
      Graphical abstract image

      PubDate: 2018-06-18T14:19:35Z
       
  • Issue TOC
    • Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79


      PubDate: 2018-06-18T14:19:35Z
       
  • Novel γ-lactone derivatives from Trigonostemon heterophyllus with their
           potential antiproliferative activities
    • Authors: Yan-Ping Liu; Shi Qing Wen Yan-Lei Zhi-Hua Jiang Jin-Ying Tang
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Yan-Ping Liu, Shi Hu, Qing Wen, Yan-Lei Ma, Zhi-Hua Jiang, Jin-Ying Tang, Yan-Hui Fu
      Two novel γ-lactone derivatives, trigoheterophines A (1) and B (2), together with four known furan derivatives (3–6), were isolated from the stems and leaves of Trigonostemon heterophyllus. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A (1) and B (2) represent an unusual type of γ-lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds (3–6) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.28 to 12.06 μM. These findings suggest that the discoveries of these novel γ-lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents.
      Graphical abstract image

      PubDate: 2018-05-28T13:41:26Z
       
  • Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and
           anticancer agents
    • Authors: Rina Soni; Shubhangi Soman
      Abstract: Publication date: September 2018
      Source:Bioorganic Chemistry, Volume 79
      Author(s): Rina Soni, Shubhangi S. Soman
      DPP-IV “a moonlighting protein” has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC50 value 24 ± 0.1 nM against A549 cell line.
      Graphical abstract image

      PubDate: 2018-05-28T13:41:26Z
       
  • Identification of Novel Indole Based Heterocycles as Selective Estrogen
           Receptor Modulator
    • Authors: Ramit Singla; Kunal Prakash; Kunj Bihari Gupta; Shishir Upadhyay; Monisha Dhiman; Vikas Jaitak
      Abstract: Publication date: Available online 24 April 2018
      Source:Bioorganic Chemistry
      Author(s): Ramit Singla, Kunal Prakash, Kunj Bihari Gupta, Shishir Upadhyay, Monisha Dhiman, Vikas Jaitak
      In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-α competitor assay kit by utilizing estrogen receptor-α (ER-α) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-α, thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5c and 6d represent novel ER-α antagonists and may be used in the development of chemotherapy for the management of BC.
      Graphical abstract image

      PubDate: 2018-04-25T03:18:51Z
      DOI: 10.1016/j.bioorg.2018.04.002
       
  • Semicarbazone Derivatives as Urease Inhibitors: Synthesis, Biological
           Evaluation, Molecular Docking Studies and In-Silico ADME Evaluation
    • Authors: Syeda Uroos Qazi; Shafiq Ur Rahman; Asia Naz Awan; Mariya al-Rashida; Rima D. Alharthy; Asnuzilawati Asari; Abdul Hameed; Jamshed Iqbal
      Abstract: Publication date: Available online 18 April 2018
      Source:Bioorganic Chemistry
      Author(s): Syeda Uroos Qazi, Shafiq Ur Rahman, Asia Naz Awan, Mariya al-Rashida, Rima D. Alharthy, Asnuzilawati Asari, Abdul Hameed, Jamshed Iqbal
      A series of hydrazinecarboxamide derivatives were synthesized and examined against urease for their inhibitory activity. Among the series, the 1-(3-fluorobenzylidene)semicarbazide (4a) (IC50 = 0.52 ± 0.45 µM), 4u (IC50= 1.23 ± 0.32 µM) and 4h (IC50=2.22 ± 0.32 µM) were found most potent. Furthermore, the molecular docking study was also performed to demonstrate the binding mode of the active hydrazinecarboxamide with the enzyme urease. In order to estimate drug likeness of compounds, in-silico ADME evaluation was carried out. All compounds exhibited favorable ADME profiles with good predicted oral bioavailability.
      Graphical abstract image

      PubDate: 2018-04-25T03:18:51Z
      DOI: 10.1016/j.bioorg.2018.03.029
       
 
 
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