Blar i forfatter "Sylte, Ingebrigt"

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    • Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds 

      Rahman, Fatema; Nguyen, Tra-Mi; Adekoya, Olayiwola; Campestre, Cristina; Tortorella, Paolo; Sylte, Ingebrigt; Winberg, Jan-Olof (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-23)
      Compounds containg catechol or bisphosphonate were tested as inhibitors of the zinc metalloproteases, thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) which are bacterial virulence factors, and the human matrix metalloproteases MMP-9 and −14. Inhibition of virulence is a putative strategy in the development of antibacterial drugs, but the inhibitors should not interfere with human enzymes. ...

    • Ligand-guided homology modelling of the GABAb2 subunit of the GABAb receptor 

      Freyd, Thibaud; Warszycki, Dawid; Mordalski, Stefan; Bojarski, Andrzej J; Sylte, Ingebrigt; Gabrielsen, Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-21)
      γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and disturbances in the GABAergic system have been implicated in numerous neurological and neuropsychiatric diseases. The GABA<sub>B</sub> receptor is a heterodimeric class C G protein-coupled receptor (GPCR) consisting of GABA<sub>B1a/b</sub> and GABA<sub>B2</sub> subunits. Two GABA<sub>B</sub> receptor ...

    • A linear combination of pharmacophore hypotheses as a new tool in search or new active compounds - An application for 5-HT1a receptor ligands 

      Warszycki, Dawid; Mordalski, Stefan; Kristiansen, kurt; Kafel, Rafal; Sylte, Ingebrigt; Chilmonczyk, Zdzislaw; Bojarski, Andrzej J. (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      This study explores a new approach to pharmacophore screening involving the use of an optimized linear combination of models instead of a single hypothesis. The implementation and evaluation of the developed methodology are performed for a complete known chemical space of 5-HT1AR ligands (3616 active compounds with Ki < 100 nM) acquired from the ChEMBL database. Clusters generated from three different ...

    • Mass-spectrometric studies of new 6-nitroquipazines-serotonin transporter inhibitors 

      Witowska-Jarosz, Janina; Jaronczyk, Malgorzata; Mazurek, Aleksander P; Sylte, Ingebrigt; Bojarski, Andrezej J; Chilmonczyk, Zdzislaw; Jarosz, Maciej (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      Six synthesized 6-nitroquipazine derivatives were examined by electron ionization (EI) and electrospray ionization (ESI) mass spectrometry in positive and negative ion mode. The compounds exhibit high affinity for the serotonin transporter (SERT) and belong to a new class of SERT inhibitors. The EI mass spectra registered in negative ion mode showed prominent molecular ions for all the compounds ...

    • Molecular Interactions Stabilizing the Promatrix Metalloprotease-9·Serglycin Heteromer 

      Dawadi, Rangita; Malla, Nabin; Hegge, Beate; Wushur, Imin; Berg, Eli; Svineng, Gunbjørg; Sylte, Ingebrigt; Winberg, Jan-Olof (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-12)
      Previous studies have shown that THP-1 cells produced an SDS-stable and reduction-sensitive complex between proMMP-9 and a chondroitin sulfate proteoglycan (CSPG) core protein. The complex could be reconstituted in vitro using purified serglycin (SG) and proMMP-9 and contained no inter-disulfide bridges. It was suggested that the complex involved both the FnII module and HPX domain of proMMP-9. The ...

    • Molecular model of the outward facing state of the human P-glycoprotein (ABCB1), and comparison to a model of the human MRP5 (ABCC5) 

      Ravna, Aina W.; Sylte, Ingebrigt; Sager, Georg (Journal article; Tidsskriftartikkel; Peer reviewed, 2007-09-06)
      Background: Multidrug resistance is a particular limitation to cancer chemotherapy, antibiotic treatment and HIV medication. The ABC (ATP binding cassette) transporters human P-glycoprotein (ABCB1) and the human MRP5 (ABCC5) are involved in multidrug resistance. Results: In order to elucidate structural and molecular concepts of multidrug resistance, we have constructed a molecular model of the ...

    • Molecular modelling, synthesis, and biological evaluations of a 3,5-disubstituted isoxazole fatty acid analogue as a PPARα-selective agonist 

      Arnesen, Henriette; Haj-Yasein, Nadia N.; Tungen, Jørn E.; Soedling, Helen; Matthews, Jason; Paulsen, Steinar M.; Nebb, Hilde I.; Sylte, Ingebrigt; Hansen, Trond Vidar; Sæther, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-19)
      The peroxisome proliferator activated receptors (PPARs) are important drug targets in treatment of metabolic and inflammatory disorders. Fibrates, acting as PPARα agonists, have been widely used lipid-lowering agents for decades. However, the currently available PPARα targeting agents show low subtype-specificity and consequently a search for more potent agonists have emerged. In this study, previously ...

    • Proposal of selective inhibitor for bacterial zinc metalloprotease: Molecular mechanics and ab initio molecular orbital calculations 

      Imai, Kyohei; Saito, Rysouke; Ezawa, Takyua; Sugiyama, Satoshi; Sylte, Ingebrigt; Kurita, Noriyuki (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-10-11)
      The zinc metalloprotease pseudolysin (PLN) secreted from Pseudomonas aeruginosa degrades extracellular proteins to produce bacterial nutrition, and various types of PLN inhibitors have been developed to suppress the bacterial growth. However, as the structure of the ligand-binding pocket of PLN has large similarities to those of human matrix metalloproteinases (MMPs) and other human zinc metalloprotease, ...

    • Protonation states of central amino acids in a zinc metalloprotease complexed with inhibitor: Molecular mechanics optimizations and ab initio molecular orbital calculations 

      Ezawa, Takuya; Saito, Ryosuke; Suzuki, Shusuke; Sugiyama, Satoshi; Sylte, Ingebrigt; Kurita, Noriyuki (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-04-01)
      The zinc-metalloprotease pseudolysin (PLN) secreted from bacteria degrades extracellular proteins to produce bacterial nutrition. Since PLN has a Zn ion at the inhibitor-binding site, the interactions between Zn and PLN residues as well as inhibitor can be significantly changed depending on the protonation states of PLN residues at the inhibitor-binding site. To determine stable protonation states ...

    • The selectivity of galardin and an azasugar-based hydroxamate compound for human Matrix metalloproteases and bacterial metalloproteases 

      Sylte, Ingebrigt; Dawadi, Rangita; Malla, Nabin; von Hofsten, Susannah; Nguyen, Tra-Mi; Solli, Ann Iren; Berg, Eli; Adekoya, Olayiwola A.; Svineng, Gunbjørg; Winberg, Jan-Olof (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-03)
      Inhibitors targeting bacterial enzymes should not interfere with enzymes of the host, and knowledge about structural determinants for selectivity is important for designing inhibitors with a therapeutic potential. We have determined the binding strengths of two hydroxamate compounds, galardin and compound 1b for the bacterial zinc metalloproteases, thermolysin, pseudolysin and auerolysin, known to ...

    • Specific interactions between the alkaline protease of P. aeruginosa and its natural peptide inhibitor: ab initio molecular simulations 

      Saito, Ryosuke; Imai, Kyohei; Yamamoto, Shohei; Ezawa, Takuya; Sugiyama, Satohsi; Evenseth, Linn; Sylte, Ingebrigt; Kurita, Noriyuki (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-16)
      Alkaline protease aeruginolysin (APR) is an important virulence factor in the evasion of the immune system by Pseudomonas aeruginosa (P. aeruginosa). The P. aeruginosa genome also encodes the highly potent and specifc APR peptide inhibitor (APRin). However, the structural reason for the signifcant inhibition has not been revealed. Using ab initio molecular simulations, we here investigated the ...

    • Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A&lt;sub&gt;2&lt;/sub&gt;, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines 

      Jantan, Ibrahim; Bukhari, Syed Nasir Abbas; Adekoya, Olayiwola; Sylte, Ingebrigt (Journal article; Tidsskriftartikkel; Peer reviewed, 2014-09-16)
      Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities ...

    • Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations 

      Gabrielsen, Mari; Ravna, aina westrheim; Kristiansen, kurt; Sylte, Ingebrigt (Journal article; Tidsskriftartikkel; Peer reviewed, 2011-06-14)
      The serotonin (5-HT) transporter (SERT) plays an important role in the termination of 5-HT-mediated neurotransmission by transporting 5-HT away from the synaptic cleft and into the presynaptic neuron. In addition, SERT is the main target for antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs). The three-dimensional (3D) structure of SERT has not yet been determined, ...

    • Synthesis, biological evaluation and molecular modeling of new analogs of the anti-cancer agent 2-methoxyestradiol: potent inhibitors of angiogenesis 

      Solum, Eirik Johansson; Cheng, Jing-Jy; Sylte, Ingebrigt; Vik, Anders; Hansen, Trond Vidar (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-03-27)
      The synthesis, cytotoxicity, inhibition of tubulin polymerization and anti-angiogenic effects of 10 analogs of 2-methoxyestradiol are reported. These efforts revealed that the analog with a 4-pyridine ring in the 17-position, in combination with 2-ethyl- and 3-sulfamate substituents on the steroid A-ring, is the most interesting anti-cancer agent. This compound showed potent inhibitory effects against ...

    • Synthesis, biological evaluation and molecular modeling studies of the PPARβ/δ antagonist CC618 

      Kaupang, Åsmund; Paulsen, Steinar Martin; Steindal, Calin Constantin; Ravna, Aina Westrheim; Sylte, Ingebrigt; Halvorsen, Trine Grønhaug; Thoresen, G. Hege; Hansen, Trond Vidar (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-03-05)
      Abstract: Herein, we describe the synthesis, biological evaluation and molecular docking of the selective PPARb/ d antagonist (4-methyl-2-(4-(trifluoromethyl)phenyl)-N-(2-(5-(trifluoromethyl)-pyridin-2-ylsulfonyl) ethyl)thiazole-5-carboxamide)), CC618. Results from in vitro luciferase reporter gene assays against the three known human PPAR subtypes revealed that CC618 selectively antagonizes ...

    • Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors 

      Sjøli, Stian; Nuti, Elisa; Camodeca, Caterina; Bilto, Irina; Rossello, Armando; Winberg, Jan-Olof; Sylte, Ingebrigt; Adekoya, Olayiwola (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-28)
      Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated ...

    • Synthesis, in vitro and in vivo biological evaluation of new oxysterols as modulators of the liver X receptors 

      Åstrand, Ove Alexander Høgmoen; Viktorsson, Elvar Örn; Kristensen, Aleksander Lim; Ekeberg, Dag; Røberg-Larsen, Hanne; Wilson, Steven Ray Haakon; Gabrielsen, Mari; Sylte, Ingebrigt; Rustan, Arild; Thoresen, G. Hege; Rongved, Pål; Kase, Eili Tranheim (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-07-26)
      Liver X Receptor (LXR) modulators have shown potential as drugs since they target genes affecting metabolism and fatty acid synthesis. LXR antagonists are of particular interest since they are able to reduce the synthesis of complex fatty acids and glucose uptake. Based on molecular modeling, five new cholesterol mimics were synthesized, where four contained a hydroxyl group in the 22-S-position. ...

    • Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases 

      Rahman, Fatema; Wushur, Imin; Malla, Nabin; Åstrand, Ove Alexander Høgmoen; Rongved, Pål; Winberg, Jan-Olof; Sylte, Ingebrigt (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-22)
      Inhibition of bacterial virulence is believed to be a new treatment option for bacterial infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc metalloproteases, ...