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Smith, V; Hovland, R; Rongved, Pål & Økstad, Ole Andreas
(2023).
Preclinical development of a novel metallo-β-lactamase inhibitor APC148.
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Viktorsson, Elvar Örn; Åstrand, Ove Alexander Høgmoen; Bonge-Hansen, Tore; Doskeland, Stein Ove; Herfindal, Lars & Rongved, Pål
(2016).
Total synthesis and initial antileukemic evaluation of the phenazine 5,10-dioxide natural products iodinin and myxin.
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Åstrand, Ove Alexander Høgmoen; Schnaars, Christian; Kildahl-Andersen, Geir & Rongved, Pål
(2016).
Overcoming b-lactam resistance - A potential solution to antibiotic resistance.
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Åstrand, Ove Alexander Høgmoen & Rongved, Pål
(2015).
OVERCOMING ANTIBIOTIC RESISTANCE - DEVELOPMENT OF NEW MBL INHIBITORS.
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Grøthe, Bendik Melling; Snellingen, Simen; Viktorsson, Elvar Örn; Prandina, Anthony; Åstrand, Ove Alexander Høgmoen & Bonge-Hansen, Tore
[Vis alle 7 forfattere av denne artikkelen]
(2015).
The first efficient synthesis and preliminary biological effect of the 1,6-dihydroxyphenazine-N5,N10-dioxide (Iodinin) and 1-hydroxy-6-methoxyphenazine-N5,N10-dioxide (Myxin).
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Prandina, Anthony; Frøvold, Espen; Åstrand, Ove Alexander Høgmoen & Rongved, Pål
(2015).
Synthetic efforts towards new agents against resistant bacteria.
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Åstrand, Ove Alexander Høgmoen; Leiros, Hanna-Kirsti S.; Samuelsen, Ørjan; Bayer, Annette & Rongved, Pål
(2015).
Overcoming b-lactam resistance - A potential solution to multi-drug resistant bacteria.
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Viktorsson, Elvar Örn; Åstrand, Ove Alexander Høgmoen; Rustan, Arild; Thoresen, G. Hege; Kase, Eili Tranheim & Rongved, Pål
(2015).
Analogs of 22-S-hydroxycholesterol as potential Liver X Receptor-modulators: Synthesis and biological evaluation.
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Haseeb, Rasha Sabah; Viktorsson, Elvar Örn; Åstrand, Ove Alexander Høgmoen & Rongved, Pål
(2015).
Synthetic efforts towards oxysterol-based LXR-modulators.
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Skagseth, Susann; Carlsen, Trine Josefine Olsen; Akhter, Sundus; Zeeshan, Muhammad; Åstrand, Ove Alexander Høgmoen & Bayer, Annette
[Vis alle 9 forfattere av denne artikkelen]
(2015).
The fight against metallo-beta-lactamases and antibiotic resistance.
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Skagseth, Susann; Carlsen, Trine Josefine Olsen; Akhter, Sundus; Zeeshan, Muhammad; Åstrand, Ove Alexander Høgmoen & Bayer, Annette
[Vis alle 9 forfattere av denne artikkelen]
(2015).
The fight against metallo-beta-lactamases and antibiotic resistance.
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Skagseth, Susann; Carlsen, Trine Josefine Olsen; Christopeit, Tony; Akhter, Sundus; Zeeshan, Muhammad & Åstrand, Ove Alexander Høgmoen
[Vis alle 10 forfattere av denne artikkelen]
(2015).
The fight against metallo-beta-lactamases and antibiotic resistance.
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Bækkelund Langgård, Øyvind; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute
(2014).
Preparing Liver X Receptors for Structural Studies.
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Bækkelund Langgård, Øyvind; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute
(2013).
Preparing Liver X Receptor for Structural Studies.
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Bækkelund Langgård, Øyvind; Grøthe, Bendik H.; Bousquet, Paula; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute
(2013).
Preparing Liver X Receptors for Structural Studies.
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Tina, Elvestrand; Åstrand, Ove Alexander; Smith, Robert; Rongved, Pål; Nilsen, Hilde & Solberg, Rigmor
[Vis alle 7 forfattere av denne artikkelen]
(2013).
Cellular effects of a colchicine-prodrug cleaved by legumain.
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Åstrand, Ove Alexander; Hansen, Trond Vidar & Rongved, Pål
(2011).
Synthesis of new zinc2+ chelating molecules.
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Åstrand, Ove Alexander; Hansen, Trond Vidar & Rongved, Pål
(2010).
Development of new selctive chelating agents for zinc.
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Klaveness, Jo & Rongved, Pål
(2008).
Smør deg inn med Omega 3.
[Avis].
NRK Nordland.
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Klaveness, Jo & Rongved, Pål
(2008).
Har knekt omega-3-koden.
[Internett].
Forskning.no.
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Jacobsen, Øyvind; Klaveness, Jo; Ottersen, Ole Petter; Mahmood reza, Amiry-Moghaddam & Rongved, Pål
(2008).
Synthesis of cyclic peptide analogues of the 310 helical Pro138-Gly144 segment of human aquaporin-4 by olefin metathesis.
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Jynge, Per; Brurok, Heidi; Nordhøy, Wibeke; Rongved, Pål & Karlsson, Jan O G
(2006).
Manganese agents in cardiac MRI and in cardioprotection.Per Jynge, Heidi Brurok, Wibeke Nordhøy, Pål Rongved, and Jan OG Karlsson.
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Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar
(2006).
Synthesis and 15-LO inhibitory activity of triazoles derived from Combretastatin A-4.
Vis sammendrag
Combretastatins belong to a class of natural products isolated from the South African tree Combretum caffrum. This class of compounds has been identified as competitive inhibitors of the colchicine binding site on β-tubulin. One of the most active compounds in this class of natural products is combretastatin A-4 (1). The non-complex structures and high affinity of combretastatins for the colchicine binding site make the combretastatins attractive lead compounds in the development of new tubulin inhibitors.
Thus, novel compounds derived from the combretastatin family are of interest as anticancer agents. We want to replace the olefinic moiety with a 1,4-disubstitiuted 1,2,3-
triazole.
Introduction of this 5-membered heterocycle will offer the following advantages:
1) no isomerization of the double bond
2) increased biological specificity since the trans isomer might be recognized by other cellular targets
3) introduction of a heterocyclic system may have improved therapeutic potential
4) enhanced stability since phenanthrene formation is avoided
Furthermore, the presence of one or several phenolic hydroxyl groups and methyl ethers in the combretastatins spurred our interest in examining their ability to scavenge radicals and inhibit lipoxygenases, since radicals are important in the development of cancer and atherosclerosis.
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Rongved, Pål
(2005).
Forskningsbasert Innovasjon.
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Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar
(2005).
Synthesis and biological activity of combretastatin derivatives.
Vis sammendrag
Combretastatins belong to a class of natural products isolated from the South African tree Combretum caffrum. This class of compounds has been identified as competitive inhibitors of the colchicine binding site on β-tubulin. The non-complex structures and high affinity of combretastatins for the colchicine binding site make the combretastatins attractive lead compounds in the development of new tubulin inhibitors. Thus, novel compounds derived from the combretastatin family are of interest as anticancer agents. Furthermore, the presence of one or several phenolic hydroxyl groups and methyl ethers in the combretastatins spurred our interest in examining their ability to scavenge radicals and inhibit lipoxygenases, since radicals are important in the development of cancer and atherosclerosis.
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Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar
(2005).
Synthesis of Combretastatin A-1 and B-1.
Vis sammendrag
The microtubules play an important role among cellular structures necessary to maintain growth and function of normal ang malignant cells since they are essential components of cell structure, and are involved in many important cellular processes including mitosis, morphogenesis, intracellular transport and secretion. Tubulin, the basic subunit of microtubules, is composed of an α,β-heterodimer. The polymerization of this heterodimer complex leads to microtubule formation. The binding of small molecules and other proteins to tubulin can result in the stabilization or destabilization of microtubule formation.
Compounds such as taxoids and vinca alkaloids, which interact with the α-domains on tubulin, have been synthesized and evaluated as tubulin inhibitors. However, their complex structures and demanding syntheses have limited Structural Activity Studies (SAR). Furthermore, these structurally complex natural products exhibit limited bioavailability.
Combretastatins belong to a class of natural products isolated from the South African tree Combretum caffrum. This class of compounds has been identified as competitive inhibitors of the colchicine binding site on β-tubulin.
We wish to report an efficient synthesis of Combretastatin A-1 and B-1.
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Rongved, Pål
(2005).
Hva betyr det for de norske TTO-kontorene (Technology Transfer Office) at Norge ikke er med i EPO ?
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Solberg, Jan; Redford, Keith; Rongved, Pål & Klaveness, Jo
(1994).
Polymere, biodegraderbare ved enzymkatalyse, for medisinske anvendelser.
Kjemi.
ISSN 0023-1983.
54(8),
s. 26–27.
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Olsen, Christine; Wilson, Steven Ray Haakon; Skottvoll, Frøydis Sved; Brandtzaeg, Ole Kristian; Rongved, Pål & Lundanes, Elsa
(2019).
Synthesis and immobilization of linked Wnt-signaling pathway inhibitor on organic monoliths as a proof-of-concept of a capti remedium ad monolitus reactor for online drug deconvolution.
Universitetet i Oslo.
Vis sammendrag
A challenge in drug discovery is the identification of the drug target, called drug deconvolution. Additionally, off-target effects are considered as one of the reasons many developed drugs fail in the clinical trials. The goal of this work was to develop a solid support, displaying low secondary interactions, for immobilization of drugs (named by author as a CRAM reactor) suitable for incorporation online liquid chromatography mass spectrometry set-ups. The hypothesis was that selective purification on the online reactor would allow identification of low abundant drug targets as a consequence of reduced handling time, contamination and loss of the sample. As a proof-of-concept, an ethylene dimethacrylate-co-vinyl azlactone (EDMA-co-VDM) monolith, prepared in 180 µm inner diameter (ID) or 250 µm ID polyimide-coated fused silica capillaries, would be immobilized with Wnt-signaling pathway inhibitor 161. The 161-immobilized CRAM reactor would then attempt to selectively trap and release a low abundant protein target, tankyrase 2 (TNKS2). The EDMA-co-VDM monolith was successfully prepared in 250 µm ID capillaries. The Wnt-inhibitor 161 was rejected based on MS characterization and LDW639, a structural analogue of Wnt-inhibitor XAV939, was successfully synthesized by the author. To improve availability of LDW639 after immobilization, a linker was attached to LDW639 during synthesis. The linked LDW639 showed 50% inhibition of the Wnt-signaling pathway at a concentration of 11 µM after 24 hours incubation in cells. The EDMA-co-VDM monolith showed secondary interactions towards proteins, but the issues were resolved by quenching the reactive VDM monomer with either monoethanolamine (MEA) or an excess of linked LDW639. Immobilization of the linked LDW639 was found to be successful based on measured UV-Vis absorbance of solutions containing LDW639 was reduced by flushing a monolith, but not by monoliths already flushed with MEA (MEA monolith). The linked LDW639-immobilized CRAM reactors and the MEA monolith were not able to trap and release TNKS1/2 from human embryonic kidney 293 cells after cell lysis with a non-denaturing buffer. Showing that the identification of the drug target from complex matrices remained a challenge, even with tailored materials.
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Berntsen, Linn Neerbye; Hansen, Tore Bonge & Rongved, Pål
(2018).
Rh(II)-catalyzed cyclopropanation-ring expansion of 7-azaindoles with halodiazoacetates and indoles with halodiazophosphonates.
Universitetet i Oslo.
Vis sammendrag
Up until now, the antibacterial 8-azaquinolones have been prepared using various ring-closing reactions. This work demonstrates the attempted synthesis of 8-azaquinolone antibacterial agents using a synthetic route that involves a reaction recently developed in our group. The reaction is considered the key step of the synthesis and allows for the transformation of 7-azaindoles to 8-azaquinoline-3-carboxylates via a Rh(II)-catalyzed cyclopropanation-ring expansion reaction with ethyl halodiazoacetates. No 8-azaquinolone antibacterial agent was successfully synthesized from 7-azaindoles using this reaction due to decomposition of an intermediate product. The majority of the time was spent on optimization of the reaction conditions as the major product turned out to be the undesired N-H-insertion product. With the new, optimized conditions, reproducibility was seemingly an issue. Even so, some already reported and some novel 8-azaquinolines were successfully synthesized in modest to good yields. The chemistry and transformations of halodiazophosphonates have not been extensively investigated. For that reason, it was of large interest to investigate if they could participate in the same cyclopropanation-ring expansion reactions as the halodiazoacetates, and further be used in synthesis towards a bioisoster of a (fluoro)quinolone antibacterial agent. In this part of the work, the successful generation and isolation of diethyl halodiazophosphonates, and the generation of quinolinyl-3-phosphonates from indoles and diethyl halodiazophosphonates is described. The reaction was investigated for a series of indole derivatives with substituents in selected positions. The majority of the reactions afforded the desired product in modest to good yields. Except for one product, the 3-quinolinyl-phosphonates described are synthesized and isolated here for the first time. Purification and isolation of these compounds on silica gel proved to be troublesome due to tailing of the products and traces of several byproducts. No bioisoster of a (fluoro)quinolone was successfully synthesized as the investigation of the indole series revealed that the reaction was not compatible with the required substitution pattern. Both diazo compounds used throughout this work were halogenated according to a procedure developed in our group. The successful quantification of the halogenated ethyl halodiazoacetates where excellent yields were afforded is also described in this work. The same success was not obtained in the quantitative analysis of the halogenated diazophosphonates due to a large degree of varying yields.
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Grøthe, Bendik Melling; Bonge-Hansen, Tore & Rongved, Pål
(2015).
Syntese av myxin og myxinderivater som potensielle legemidler mot akutt myelogen leukemi.
Universitetet i Oslo.
Vis sammendrag
Naturproduktet myxin er et potensielt nytt legemiddel mot akutt myelogen leukemi (AML). Myxin er praktisk talt uløselig i vann, og frem til idag er det ikke rapportert noen effektiv syntese av dette naturproduktet. En målsetning for dette prosjektet har vært å utvikle en ny og effektiv synteserute til myxin, samt syntetisere derivater med økt løselighet i polare løsningsmidler. To synteseruter har blitt undersøkt, og en 4-trinns synteserute til myxin har blitt etablert med 35% totalt utbytte. Som en del av denne synteseruten har også en synteserute til naturproduktet iodinin (2a) blitt utviklet med 57% totalt utbytte. Flere prosedyrer for syntese av forskjellige myxinderivater har blitt testet, og fire nye derivater har blitt syntetisert med gode utbytter. Myxin har blitt biologisk testet og preliminære resultater er presentert i denne oppgaven.
The natural product myxin is a potential new drug against acute myeloid leukemia (AML). Myxin is practically insoluble in water, and up until today, an effective synthesis of this natural product has not been reported. Among the aims of this project, one has been to develop a new and efficient route of synthesis of myxin and to synthesize derivatives of the product with increased solubility in polar solvents. Two routs of synthesis have been studied, and one four-step route to myxin has been established with a total yield of 35%. As a part of this synthesis, a route of synthesis to the natural compound iodinin has also been developed; this with a total yield of 57%. Several procedures for synthesis of different derivatives of myxin have been tested, and four new derivatives have been synthesized with satisfying yields. Myxin has been biologically testes and preliminary results are presented in this thesis.
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