Pål Rongved

• Pham, Aina Kristin; Hiorth, Marianne & Rongved, Pål (2025). A novel and stable formulation of powdered high-assay calcium hypochlorite as a solid precursor of the antimicrobial compound hypochlorous acid: a preformulation study. Journal of Drug Delivery Science and Technology. ISSN 1773-2247. 113. doi: 10.1016/j.jddst.2025.107292. Fulltekst i vitenarkiv Vis sammendrag

  Hypochlorous acid (HOCl) has been strongly recognized in the wake of the COVID-19 pandemic. It is a well-known antimicrobial compound with a broad-spectrum effect that demonstrates excellent clinical safety results in wounds. However, stable HOCl products remain unavailable due to challenges in maintaining storage stability, particularly at higher concentrations (≥200 μg g−1) at room temperature. To address this limitation, we investigated calcium hypochlorite (Ca[OCl]2) as a stable solid precursor for in-situ HOCl generation. This paper presents comprehensive preformulation characterization data, including powder stability analysis and release kinetics, establishing the foundational parameters necessary for future product development. We have demonstrated that commercial Ca(OCl)2 granules dissolves in a buffered medium and converts to HOCl at the time of use. However, the granules convert too slowly and may jeopardize user-friendliness. Through a mixed multivariate experimental design, we found that grinding the granules into a powder (particle sizes between 45 and 500 μm) significantly improved the conversion rates, achieving ≥99.4 % conversion within 10 s of shaking in acetic acid buffer pH 4.3 for samples equivalent to 2000 μg g−1 HOCl. Particles sized 125–150 and 180–250 μm showed rapid dissolution, with ≥98.4 % conversion within just 1 s of shaking. Powdered Ca(OCl)2 was stable for at least 24 months at 23 °C ± 2 when stored dry (≤5 % degradation), though higher temperatures and moisture negatively affected the storage stability. Flow behavior of powdered Ca(OCl)2 was also studied by the angle of repose, Hausner's ratio and compressibility index for future production purposes of the novel formulation. Good flow was observed for powders above 250 μm in particle size, whereas the tests failed for particle size below 150 μm. In summary, these findings demonstrate that powdered Ca(OCl)2 is highly stable under the proper storage conditions, making it a promising and novel HOCl precursor formulation for combating bacterial biofilm and other topical microbial infections.

• Reiten, Ingeborg Nerbø; Æsøy, Reidun; Førde, Jan-Lukas; Khose, Goraksha Machhindra; Viktorsson, Elvar Örn & Bruserud, Øystein [Vis alle 9 forfattere av denne artikkelen] (2025). Phenazine 5,10-dioxide analogues as potential therapeutics in AML: Efficacy on patient-derived blasts, in zebrafish larvae xenografts and synergy with venetoclax. Translational Oncology. ISSN 1944-7124. 63. doi: 10.1016/j.tranon.2025.102628. Fulltekst i vitenarkiv Vis sammendrag

  Although several new therapies against acute myeloid leukaemia (AML) have emerged the past years, patients who are ineligible for intensive chemotherapy are still treated with less effective treatments to minimise therapy-associated mortality. Several phenazine 5,10-dioxide derivates have previously demonstrated to selectively induce apoptosis in human AML cells. In the present work, we have continued investigations on phenazine 5,10-dioxides to reveal their therapeutic potential in AML using in vitro and in vivo experiments. From a panel of primary AML blasts from 61 non-selected patients, 58 showed high or intermediate response to treatment with the phenazine 5,10-dioxides. This included blasts with biological characteristics associated with poor prognosis, such as FLT3 internal tandem duplication, NPM-1 wild type, CD34+, and adverse cytogenetics. The phenazine 5,10-dioxides cytotoxicity towards primary blasts correlated with the blast’s sensitivity to daunorubicin, presumably due to similar mode of action towards AML cells. Three phenazine 5,10-dioxides had low toxicity in zebrafish larvae, and from these, two were found effective towards zebrafish larvae AML xenografts. Additionally, synergism with the AML drug venetoclax (VTX) was found in the AML cell lines MOLM-13 and MV4–11. The efficacy of phenazine 5,10-dioxides towards primary AML blasts, synergism with VTX and low toxicity in effective concentrations in zebrafish larva AML xenografts suggests potential for these compounds in future AML therapy for patients unfit for intensive chemotherapy.

• Hovd, Rebekka Rolfsnes; Kaupang, Åsmund; Rongved, Pål; Kildahl-Andersen, Geir; Hylland, Knut Tormodssønn & Hovland, Ragnar [Vis alle 9 forfattere av denne artikkelen] (2025). APC24-7, a covalent combination of boronic acid and chelator moieties, restores β-lactam efficiency against metallo-β-lactamase-producers. mSphere. 10(12). doi: 10.1128/msphere.00418-25. Fulltekst i vitenarkiv Vis sammendrag

  β-Lactam/β-lactamase inhibitor combinations have significantly improved treatment outcomes for infections caused by serine β-lactamase (SBL)-producing pathogens. However, the continued emergence and spread of metallo-β-lactamases (MBLs), for which no clinically approved inhibitors currently exist, poses a serious threat to the long-term effectiveness of β-lactam-based therapies. To bridge this therapeutic gap, the boronic acid transition state analog, taniborbactam (Venatorx Pharmaceuticals), was developed, targeting SBLs and widespread MBLs such as NDM-1 and VIM-2. However, taniborbactam-escape variants have been detected among various MBL enzymes, including members of the NDM and IMP families. Here, we explored whether covalently combining two complementary inhibitor structures, a boronic acid transition state analog and a dipicolyl ethylenediamine-based metal chelator, can restore β-lactam susceptibility in MBL-producing bacterial strains, including taniborbactam-escape variants. APC24-7 successfully sensitized clinical isolates of SBL- and MBL-producing Klebsiella pneumoniae and Escherichia coli to meropenem. While APC24-7 demonstrated similarities in resensitization behavior to taniborbactam against a wide range of isogenic E. coli expressing single SBLs, APC24-7 reversed NDM-9- or IMP-26-mediated meropenem resistance more efficiently. To investigate the potential role of the chelator motif in the MBL inhibition of APC24-7, susceptibility tests were conducted with an excess of exogenous Zn² + . APC24-7-mediated resensitization remained unaffected in the presence of Zn² + for strains producing NDM-1 and VIM-2. However, its ability to reverse NDM-9- and IMP-26-mediated meropenem resistance was attenuated upon Zn² + supplementation. These findings demonstrate that combining functionally complementary chemical structures, such as chelators and boronic acids, can aid in expanding the resensitization ability of existing β-lactamase inhibitors. IMPORTANCE The ability of bacteria such as Klebsiella pneumoniae and Escherichia coli to circumvent antimicrobial chemotherapy has become a global public health crisis. The high prevalence of β-lactamase enzymes capable of rendering our most prescribed antibiotics, the β-lactams (BLs) inactive, has left us with few available treatment options against infections caused by these bacteria. The use of small molecules that inhibit especially serine β-lactamases has substantially prolonged the lifetime of BL antibiotics. Yet, most clinically available inhibitors either do not possess or have limited ability to reverse resistance conferred by metallo-β-lactamase (MBL) enzymes. Combining chelator and transition state analog technology, our hybrid compound restores the effectiveness of BL antibiotics in cases of resistance conferred by both serine β-lactamases (SBLs) and MBLs. Our approach of covalently combining a chelator with an existing SBL inhibitor scaffold offers a promising solution for managing life-threatening infections and prolonging the use of clinically available BLs.

• Khose, Goraksha Machhindra; Vagolu, Siva Krishna; Aesoy, Reidun; Stefánsson, Ísak Máni; Ríkhardsson, Snorri Geir & Ísleifsdóttir, Dagmar [Vis alle 12 forfattere av denne artikkelen] (2025). Functionalized regioisomers of the natural product phenazines myxin and iodinin as potent inhibitors of Mycobacterium tuberculosis and human acute myeloid leukemia cells. European Journal of Medicinal Chemistry. ISSN 0223-5234. 285. doi: 10.1016/j.ejmech.2025.117244. Fulltekst i vitenarkiv Vis sammendrag

  The natural bioactive products myxin and iodinin are phenazine 5,10-dioxides possessing potent anti-bacterial and anti-cancer activity in vitro. This work describes the synthesis and derivatization of new myxin and iodinin regioisomers, developed from 1,3-dihydroxyphenazine 5,10-dioxide. Compounds were evaluated for activity towards M. tuberculosis (Mtb) strains, a human AML cell line (MOLM-13), and two non-cancerous mammalian cell lines (NRK and H9c2). Highly potent analogs were developed having IC50 values against MTB down to 20 nM and 1.4 μM for human AML cells. 1-OH-3-O-alkyl substituted derivatives demonstrated high efficacy against Mtb and low toxicity in normal cells. 2,3-substituted regioisomers of myxin and iodinin were shown to be inactive, highlighting the importance of oxygen substituent in position 1 of the scaffold. A strong positive correlation between anti-MTB and anti-AML activity was revealed, suggesting a common mechanism of action in bacteria and cancer cells. These findings demonstrate the therapeutic potential of 1,3-O-functionalized phenazine 5,10-dioxides in chemotherapy for Mtb and AML and contribute to the structure-activity understanding of phenazine 5,10-dioxides with respect to their biological activity.

• Viktorsson, Elvar Örn; Aesoy, Reidun; Støa, Sindre; Lekve, Viola; Doskeland, Stein Ove & Herfindal, Lars [Vis alle 7 forfattere av denne artikkelen] (2021). New prodrugs and analogs of the phenazine 5,10-dioxide natural products iodinin and myxin promote selective cytotoxicity towards human acute myeloid leukemia cells. RSC Medicinal Chemistry. ISSN 2632-8682. 12:767(5), s. 767–778. doi: 10.1039/d1md00020a. Fulltekst i vitenarkiv Vis sammendrag

  Novel chemotherapeutic strategies for acute myeloid leukemia (AML) treatment are called for. We have recently demonstrated that the phenazine 5,10-dioxide natural products iodinin (3) and myxin (4) exhibit potent and hypoxia-selective cell death on MOLM-13 human AML cells, and that the N-oxide functionalities are pivotal for the cytotoxic activity. Very few structure–activity relationship studies dedicated to phenazine 5,10-dioxides exist on mammalian cell lines and the present work describes our efforts regarding in vitro lead optimizations of the natural compounds iodinin (3) and myxin (4). Prodrug strategies reveal carbamate side chains to be the optimal phenol-attached group. Derivatives with no oxygen-based substituent (–OH or –OCH3) in the 6th position of the phenazine skeleton upheld potency if alkyl or carbamate side chains were attached to the phenol in position 1. 7,8-Dihalogenated- and 7,8-dimethylated analogs of 1-hydroxyphenazine 5,10-dioxide (21) displayed increased cytotoxic potency in MOLM-13 cells compared to all the other compounds studied. On the other hand, dihalogenated compounds displayed high toxicity towards the cardiomyoblast H9c2 cell line, while MOLM-13 selectivity of the 7,8-dimethylated analogs were less affected. Further, a parallel artificial membrane permeability assay (PAMPA) demonstrated the majority of the synthesized compounds to penetrate cell membranes efficiently, which corresponded to their cytotoxic potency. This work enhances the understanding of the structural characteristics essential for the activity of phenazine 5,10-dioxides, rendering them promising chemotherapeutic agents.

• Rahman, Fatema; Wushur, Imin; Malla, Nabin; Åstrand, Ove Alexander Høgmoen; Rongved, Pål & Winberg, Jan-Olof [Vis alle 7 forfattere av denne artikkelen] (2021). Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases. Molecules. ISSN 1431-5157. doi: 10.3390/molecules27010056. Fulltekst i vitenarkiv Vis sammendrag

  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, matrix metalloprotease-9 (MMP-9) and matrix metalloprotease-14 (MMP-14). These compounds have nitrogen or sulfur as putative donor atoms for zinc chelation. In general, the compounds showed stronger inhibition of MMP-14 and PLN than of the other enzymes, with Ki values in the lower µM range. Except for DPA, none of the compounds showed significantly stronger inhibition of the virulence factors than of the human zinc metalloproteases. TPA and Zn230 were the only compounds that inhibited all five zinc metalloproteinases with a Ki value in the lower µM range. The thiophene compounds gave weak or no inhibition. Docking indicated that some of the compounds coordinated zinc by one oxygen atom from a hydroxyl or carbonyl group, or by oxygen atoms both from a hydroxyl group and a carbonyl group, and not by pyridine nitrogen as in DPA and TPA.

• Samuelsen, Ørjan; Åstrand, Ove Alexander Høgmoen; Frøhlich, Christopher; Heikal, Adam; Skagseth, Susann & Carlsen, Trine Josefine Olsen [Vis alle 17 forfattere av denne artikkelen] (2020). ZN148 Is a Modular Synthetic Metallo-beta-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo. Antimicrobial Agents and Chemotherapy. ISSN 0066-4804. 64(6). doi: 10.1128/AAC.02415-19. Fulltekst i vitenarkiv Vis sammendrag

  Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and <i>in vitro</i> clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical <i>Enterobacterales</i> strains (<i>n</i> = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing <i>Klebsiella pneumoniae</i> in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an <i>in vivo</i> mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ∼30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.

• Prandina, Anthony; Radix, Sylvie; Borgne, Marc Le; Jordheim, Lars Petter; Bousfiha, Zineb & Fröhlich, Christopher [Vis alle 11 forfattere av denne artikkelen] (2019). Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors. Tetrahedron. ISSN 0040-4020. 75(11), s. 1525–1540. doi: 10.1016/j.tet.2019.02.004. Fulltekst i vitenarkiv Vis sammendrag

  Antibiotics are key drugs in modern healthcare, especially in hospitals, where multiresistant bacteria resides and is a potential threat to human health. In the present work, a new series of adjuvants working synergistically with the carbapenem meropenem, in which a selective zinc-chelating agent was covalently linked to the small bacterial peptide D-Ala-D-Ala, was synthesized and tested against VIM-2 and NDM-1 metallo-β-lactamases (MBLs). The nature of the linker was modified in a structure-activity relationship study. Compound 1i, having an ethyl piperidine linker, lowered the MIC of meropenem from 32 to 64 mg/L to 2 and 1–2 mg/L against VIM-2- and NDM-1-producing clinical isolates, respectively. The IC50 value of 1i against VIM-2 was 9.8 and 2.2 μM after 5 and 20 min, respectively. Compound 1i also showed intrinsic toxicity against three eukaryotic human tumoral cell lines between 50 and 120 μM.

• Kildahl-Andersen, Geir; Schnaars, Christian; Prandina, Anthony; Radix, Sylvie; Borgne, Marc Le & Jordheim, Lars Petter [Vis alle 13 forfattere av denne artikkelen] (2019). Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors. MedChemComm. ISSN 2040-2503. 10(4), s. 528–537. doi: 10.1039/c8md00578h. Fulltekst i vitenarkiv
• Issa, Samar; Prandina, Anthony; Bedel, Nicolas; Rongved, Pål; Yous, Saïd & Borgne, Marc Le [Vis alle 7 forfattere av denne artikkelen] (2019). Carbazole scaffolds in cancer therapy: a review from 2012 to 2018. Journal of Enzyme Inhibition and Medicinal Chemistry. ISSN 1475-6366. 34(1), s. 1321–1346. doi: 10.1080/14756366.2019.1640692. Fulltekst i vitenarkiv
• Olsen, Christine; Skottvoll, Frøydis Sved; Brandtzaeg, Ole Kristian; Schnaars, Christian; Rongved, Pål & Lundanes, Elsa [Vis alle 7 forfattere av denne artikkelen] (2019). Investigating Monoliths (Vinyl Azlactone-co-Ethylene Dimethacrylate) as a Support for Enzymes and Drugs, for Proteomics and Drug-Target Studies. Frontiers in Chemistry. 7. doi: 10.3389/fchem.2019.00835. Fulltekst i vitenarkiv
• Peeters, Sara; Berntsen, Linn Neerbye; Rongved, Pål & Bonge-Hansen, Tore (2019). Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin. Beilstein Journal of Organic Chemistry. ISSN 2195-951X. 15, s. 2156–2160. doi: 10.3762/bjoc.15.212. Fulltekst i vitenarkiv Vis sammendrag

  We present a short and efficient way of synthesizing two synthetically versatile 4-quinolone-3-carboxylate building blocks by cyclopropanation-ring expansion of 3-chloroindoles with α-halodiazoacetates as the key step. This novel transformation was applied towards the synthesis of the antibiotic drug norfloxacin.

• Prandina, Anthony; Herfindal, Lars; Radix, Sylvie; Rongved, Pål; Doskeland, Stein Ove & Borgne, Marc Le [Vis alle 7 forfattere av denne artikkelen] (2018). Enhancement of iodinin solubility by encapsulation into cyclodextrin nanoparticles. Journal of Enzyme Inhibition and Medicinal Chemistry. ISSN 1475-6366. 33(1), s. 370–375. doi: 10.1080/14756366.2017.1421638. Fulltekst i vitenarkiv Vis sammendrag

  Phenazine is known to regroup planar nitrogen-containing heterocyclic compounds. It was used here to enhance the bioavailability of the biologically important compound iodinin, which is near insoluble in aqueous solutions. Its water solubility has led to the development of new formulations using diverse amphiphilic a-cyclodextrins (CDs). With the per-[6-desoxy-6-(3-perfluorohexylpropanethio)-2,3-di-O-methyl]- a-CD, we succeeded to get iodinin-loaded nanoformulations with good parameters such as a size of 97.9 nm, 62% encapsulation efficiency and efficient control release. The study presents an interesting alternative to optimizing the water solubility of iodinin by chemical modifications of iodinin.

• Schnaars, Christian; kildahl-Andersen, Geir; Prandina, Anthony; Popal, Roya; Radix, Sylvie & Borgne, Marc Le [Vis alle 16 forfattere av denne artikkelen] (2018). Synthesis and preclinical evaluation of TPA-based zinc chelators as metallo-β-lactamase inhibitors. ACS Infectious Diseases. 4(9), s. 1407–1422. doi: 10.1021/acsinfecdis.8b00137. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen; Viktorsson, Elvar Örn; Kristensen, Aleksander Lim; Ekeberg, Dag; Røberg-Larsen, Hanne & Wilson, Steven Ray Haakon [Vis alle 12 forfattere av denne artikkelen] (2017). Synthesis, in vitro and in vivo biological evaluation of new oxysterols as modulators of the liver X receptors. Journal of Steroid Biochemistry and Molecular Biology. ISSN 0960-0760. 165, s. 323–330. doi: 10.1016/j.jsbmb.2016.07.010. Fulltekst i vitenarkiv Vis sammendrag

  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. The new compounds were screened in vitro against several genes affecting lipid metabolism. The compound that performed best in vitro was a dimethylamide derivative of 22(S)-hydroxycholesterol and it was chosen for in vivo testing. However, the blood plasma analysis from the in vivo tests revealed a concentration lower than needed to give any response, indicating either rapid metabolism or low bioavailability.

• Viktorsson, Elvar Örn; Gabrielsen, Mari; Kumarachandran, Nugalya; Sylte, Ingebrigt; Rongved, Pål & Åstrand, Ove Alexander Høgmoen [Vis alle 7 forfattere av denne artikkelen] (2017). Regulation of liver X receptor target genes by 22-functionalized oxysterols. Synthesis, in silico and in vitro evaluations. Steroids. ISSN 0039-128X. 118, s. 119–127. doi: 10.1016/j.steroids.2016.12.003. Fulltekst i vitenarkiv
• Viktorsson, Elvar Örn; Grøthe, Bendik Melling; Aesoy, Reidun; Sabir, Misbah; Snellingen, Simen & Åstrand, Ove Alexander Høgmoen [Vis alle 11 forfattere av denne artikkelen] (2017). Total synthesis and antileukemic evaluations of the phenazine 5,10-dioxide natural products iodinin, myxin and their derivatives. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 25(7), s. 2285–2293. doi: 10.1016/j.bmc.2017.02.058. Fulltekst i vitenarkiv
• Viktorsson, Elvar Örn; Åstrand, Ove Alexander Høgmoen; Haseeb, Rasha Sabah; Gorbitz, Carl Henrik & Rongved, Pål (2015). Crystal structure of (S)-2-[(3S,8S,9S,10R,13S,14S,-17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,-12,13,14,15,16,17-tetradecahydro-1 H-cyclopenta-[a]phenanthren-17-yl]-N-methoxy-N-methylpro-panamide (Fernholz Weinreb amide). Acta Crystallographica Section E: Structure Reports Online. 71(3), s. 275–277. doi: 10.1107/S2056989015001747. Fulltekst i vitenarkiv Vis sammendrag

  The literature compound 3[beta]-hy­droxy-bis­nor-5-cholenic aldehyde is an important inter­mediate for the synthesis of new modulators of the nuclear oxysterol receptor Liver X. As part of our ongoing search for new LXR antagonists, the title compound, C24H39NO3, has proven to be an important inter­mediate in our new synthetic pathway, giving the corresponding aldehyde in high yield and in only three steps from the commercially available 3[beta]-hy­droxy-bis­nor-5-cholenic acid. The title amide crystallized with two mol­ecules in the asymmetric unit, linked into helices by O-H...O hydrogen bonds involving the hy­droxy and carbonyl groups.

• Åstrand, Ove Alexander Høgmoen; Sandberg, Marcel; Sylte, Ingebrigt; Gorbitz, Carl Henrik; Thoresen, G. Hege & Kase, Eili Tranheim [Vis alle 7 forfattere av denne artikkelen] (2014). Synthesis and initial biological evaluation of new mimics of the LXR-modulator 22(S)-hydroxycholesterol. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 22(1), s. 643–650. doi: 10.1016/j.bmc.2013.10.024. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen; Gikling, Ingveig; Sylte, Ingebrigt; Rustan, Arild; Thoresen, G. Hege & Rongved, Pål [Vis alle 7 forfattere av denne artikkelen] (2014). Development of new LXR modulators that regulate LXR target genes and reduce lipogenesis in human cell models. European Journal of Medicinal Chemistry. ISSN 0223-5234. 74, s. 258–263. doi: 10.1016/j.ejmech.2014.01.003. Fulltekst i vitenarkiv
• Smith, Robert; Åstrand, Ove Alexander Høgmoen; Nguyen, Luan Minh; Elvestrand, Tina; Hagelin, Gunnar & Solberg, Rigmor [Vis alle 8 forfattere av denne artikkelen] (2014). Synthesis of a novel legumain-cleavable colchicine prodrug with cell-specific toxicity. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 22(13), s. 3309–3315. doi: 10.1016/j.bmc.2014.04.056. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander; Iqbal, Zeshan; Sandberg, Marcel; Kase, Eili Tranheim; Gorbitz, Carl Henrik & Rongved, Pål (2013). (2S,3S)-2,6-Dimethylheptane-1,3-diol, the oxygenated side chain of 22(S)-hydroxycholestrol, and its synthetic precursor (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2,6-dimethylheptanoyl]-1,3-oxazolidin-2-one. Acta Crystallographica Section C: Crystal Structure Communications. ISSN 0108-2701. 69, s. 647–+. doi: 10.1107/S0108270113011852. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen; Gorbitz, Carl Henrik; Kristoffersen, Kenneth Aase & Rongved, Pål (2013). Acetonitrile){2-[bis(pyridin-2-ylmethyl-κ2 N)amino-κN]-N-(2,6-dimethylphenyl)acetamide-κO}(perchlorato-κO)zinc (acetonitrile){2-[bis(pyridin-2-ylmethyl-κ2 N)amino-κN]-N-(2,6-dimethylphenyl)acetamide-κO}zinc tris(perchlorate). Acta Crystallographica Section E: Structure Reports Online. 69(2), s. m112–m113. doi: 10.1107/S1600536813001396. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander; Aziz, Gul zeb; Ali, Sidra Farzand; Paulsen, Ragnhild Elisabeth; Hansen, Trond Vidar & Rongved, Pål (2013). Synthesis and initial in vitro biological evaluation of two new zinc-chelating compounds: Comparison with TPEN and PAC-1. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 21(17), s. 5175–5181. doi: 10.1016/j.bmc.2013.06.037. Fulltekst i vitenarkiv
• Arnt, Hals Petter; Sontum, Per-Christian; Holtz, Eckardt; Klaveness, Jo & Rongved, Pål (2013). In Vivo Cleavage Rate of a Dextran-Bound Magnetic Resonance Imaging Contrast Agent: Preparation and Intravascular Pharmacokinetic Characteristics in the Rabbit. Current Drug Delivery. ISSN 1567-2018. 10(1), s. 134–143. doi: 10.2174/1567201811310010019. Fulltekst i vitenarkiv
• Rongved, Pål; Kirsch, Gilbert; Bouaziz, Zouhair; Jose, Joachim & Borgne, Marc Le (2013). Indenoindoles and cyclopentacarbazoles as bioactive compounds: Synthesis and biological applications. European Journal of Medicinal Chemistry. ISSN 0223-5234. 69, s. 465–479. doi: 10.1016/j.ejmech.2013.08.049. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen; Austdal, Lars Peter Engeset; Paulsen, Ragnhild Elisabeth; Hansen, Trond Vidar & Rongved, Pål (2013). Synthesis and characterization of new selective Zn2+ fluorescent probes for functionalization: in vitro Cell imaging applications. Tetrahedron. ISSN 0040-4020. 49(40), s. 8645–8654. doi: 10.1016/j.tet.2013.07.049. Fulltekst i vitenarkiv
• Jacobsen, Øyvind; Gebreslasie, Hadgu G; Klaveness, Jo; Rongved, Pål & Gorbitz, Carl Henrik (2011). N-(tert-Butoxycarbonyl)-L-valyl-L-valine methyl ester: a twisted parallel beta-sheet in the crystal structure of a protected dipeptide. Acta Crystallographica Section C: Crystal Structure Communications. ISSN 0108-2701. 67, s. O278–O282. doi: 10.1107/S0108270111022293. Fulltekst i vitenarkiv
• Jacobsen, Øyvind; Maekawa, Hiroaki; Ge, Nien-Hui; Gorbitz, Carl Henrik; Rongved, Pål & Ottersen, Ole Petter [Vis alle 8 forfattere av denne artikkelen] (2011). Stapling of a 3(10)-Helix with Click Chemistry. Journal of Organic Chemistry. ISSN 0022-3263. 76(5), s. 1228–1238. doi: 10.1021/jo101670a. Fulltekst i vitenarkiv
• Borhaug, Hilde; Kristensen, Mette; Brudeli, Bjarne; Sontum, Per Chrisian; Klaveness, Jo & Rongved, Pål (2011). Water-soluble omega-3: A concept for purification of fish oil and nutraceuticals? European Journal of Lipid Science and Technology. ISSN 1438-7697. 113(10), s. 1235–1242. doi: 10.1002/ejlt.201000502. Fulltekst i vitenarkiv
• Hoff, Lars; Foss, Per A.; Dyrstad, Knut; Klaveness, Jo & Rongved, Pål (2011). Stabilization of gas bubbles released from water-soluble carbohydrates using amphiphilic compounds: preparation of formulations and acoustic monitoring of bubble lifetime. Journal of Surfactants and Detergents (JSD). ISSN 1097-3958. 14(4), s. 585–593. doi: 10.1007/s11743-011-1250-y. Fulltekst i vitenarkiv Vis sammendrag

  The ultrasound contrast agents Echovist® and Levovist® (Bayer AG, Schering AG, Germany) are based on the release of gas bubbles from milled α-D-galactose. In diagnostic ultrasound, for this class of contrast agents, there is a need for prolonged contrast duration. To investigate if new carbohydrate compositions could prolong the lifetime of the gas bubbles, α-D-galactose was mixed with other carbohydrates or amphiphiles with varying log P. Acoustic attenuation vs. time (390 s) area under the curve (A 390) and bubble half-time (t½) were used as measures of prolonged lifetime of gas bubbles. The products, to which 0.1% of a lipophilic carboxylic acid (5β-cholanic acid, behenic acid, and melissic acid) has been added, showed more than 5, 7 and 11 times enhancement of A 390, respectively, compared with the reference compound 2 (RC2) corresponding to the commercial product Levovist®. The half-time t ½ of the same compounds was prolonged more than 6 times compared with RC2. A partial least square (PLS) statistical analysis confirmed that, for additives, high log P carboxylic acids lead to the highest A 390. The present results bear a promise of products with a more persistent in vivo ultrasound contrast effect than the commercially available agents.

• Jacobsen, Øyvind; Klaveness, Jo & Rongved, Pål (2010). Structural and pharmacological effects of ring-closing metathesis in peptides. Molecules. ISSN 1431-5157. 15(9), s. 6638–6677. doi: 10.3390/molecules15096638. Fulltekst i vitenarkiv
• Jacobsen, Øyvind; Klaveness, Jo; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood Reza & Rongved, Pål (2009). Synthesis of cyclic peptide analogues of the 3(10) helical Pro138-Gly144 segment of human aquaporin-4 by olefin metathesis. Organic and biomolecular chemistry. ISSN 1477-0520. 7(8), s. 1599–1611. doi: 10.1039/b823559g. Fulltekst i vitenarkiv
• Høyem, Sverre; Bruheim, Skjalg; Mælandsmo, Gunhild M; Standal, Marius; Olberg, Dag Erlend & Brudeli, Bjarne [Vis alle 9 forfattere av denne artikkelen] (2009). Didanosine ester prodrugs: Synthesis, albumin binding properties and pharmacokinetic studies in rats. European Journal of Medicinal Chemistry. ISSN 0223-5234. 44(10), s. 3874–3879. doi: 10.1016/j.ejmech.2009.04.008. Fulltekst i vitenarkiv
• Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar (2006). Synthesis of combretastatins A-1 and B-1. Tetrahedron Letters. ISSN 0040-4039. 47, s. 1101–1103. Fulltekst i vitenarkiv Vis sammendrag

  Combretastatins A-1 and B-1 have been synthesized by coupling MOM-protected p-iodomethoxycatechol with 3,4,5-trimethoxyphenylacetylene in a Sonogashira reaction.

• Fossheim, Sigrid Lise; Kellar, Ken; Månsson, Stig; Colet, Jean M; Rongved, Pål & Fahlvik, Anne Kjersti [Vis alle 7 forfattere av denne artikkelen] (1999). Investigation of lanthanide-based starch particles as a model system for liver contrast agents. Journal of Magnetic Resonance Imaging. ISSN 1053-1807. 9(2), s. 295–295. Fulltekst i vitenarkiv
• Sigrid, Fossheim; Briley, Sæbø Karen; Kjersti, Fahlvik Anne; Rongved, Pål & Klaveness, Jo (1997). Low molecular weight lanthanide contrast agents: in vitro studies of mechanisms of action. Journal of Magnetic Resonance Imaging. ISSN 1053-1807. 7(1), s. 251–251. Fulltekst i vitenarkiv
• Fjeldskaar, Inger-Reidun; Rongved, Pål & Skattebøl, Lars (1987). A convenient method for the preparation of bicyclic dihydro-1,4-dioxins, dihydro-1,4-oxathiins, dihydro-1,4-dithiins and related compounds. Acta Chemica Scandinavica. ISSN 0904-213X. B41(7), s. 477–477. Fulltekst i vitenarkiv
• Aukrust, Audun; Rongved, Pål & Skattebøl, Lars (1985). The synthesis of (Z)-8-dodecen-1-ol and its acetate, pheromone components of the Oriental fruit moth (Grapholita molesta). Acta Chemica Scandinavica. ISSN 0904-213X. B39(4), s. 267–267. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Smith, V; Hovland, R; Rongved, Pål & Økstad, Ole Andreas (2023). Preclinical development of a novel metallo-β-lactamase inhibitor APC148. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Hovland, Ragnar; Kaupang, Åsmund; Frøhlich, Christopher & Huber, Sandra [Vis alle 8 forfattere av denne artikkelen] (2023). Investigating the Mechanism of Action of a Novel Dual β-Lactamase Inhibitor. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Hovland, Ragnar; Kaupang, Åsmund; Frøhlich, Christopher & Huber, Sandra [Vis alle 8 forfattere av denne artikkelen] (2023). Investigating the Mechanism of Action of a New Novel Dual β-Lactamase Inhibitor. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Klem, Bjørn; Hovland, Ragnar; Kaupang, Åsmund & Økstad, Ole Andreas Løchen [Vis alle 7 forfattere av denne artikkelen] (2022). Bacterial antimicrobial resistance mechanisms - The novel dual serine- and metallo-β-lactamase inhibitor APC247. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Klem, Bjørn; Hovland, Ragnar; Kildahl-Andersen, Geir & Kaupang, Åsmund [Vis alle 8 forfattere av denne artikkelen] (2022). The novel antimicrobial resistance breaker APC247 – a putative dual serine- and metallo-β-lactamase inhibitor. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen; Schnaars, Christian; Kildahl-Andersen, Geir & Rongved, Pål (2016). Overcoming b-lactam resistance - A potential solution to antibiotic resistance. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Prandina, Anthony; Frøvold, Espen; Åstrand, Ove Alexander Høgmoen & Rongved, Pål (2015). Synthetic efforts towards new agents against resistant bacteria. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander Høgmoen & Rongved, Pål (2015). OVERCOMING ANTIBIOTIC RESISTANCE - DEVELOPMENT OF NEW MBL INHIBITORS. Fulltekst i vitenarkiv
• Haseeb, Rasha Sabah; Viktorsson, Elvar Örn; Åstrand, Ove Alexander Høgmoen & Rongved, Pål (2015). Synthetic efforts towards oxysterol-based LXR-modulators. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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). Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Langgård, Øyvind Bækkelund; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute (2014). Preparing Liver X Receptors for Structural Studies. Fulltekst i vitenarkiv
• Langgård, Øyvind Bækkelund; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute (2013). Preparing Liver X Receptor for Structural Studies. Fulltekst i vitenarkiv
• Langgård, Øyvind Bækkelund; Grøthe, Bendik H.; Bousquet, Paula; Burschowsky, Daniel; Rongved, Pål & Krengel, Ute (2013). Preparing Liver X Receptors for Structural Studies. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander; Hansen, Trond Vidar & Rongved, Pål (2011). Synthesis of new zinc2+ chelating molecules. Fulltekst i vitenarkiv
• Åstrand, Ove Alexander; Hansen, Trond Vidar & Rongved, Pål (2010). Development of new selctive chelating agents for zinc. Fulltekst i vitenarkiv
• Jacobsen, Øyvind; Klaveness, Jo; Ottersen, Ole Petter; reza, Amiry-Moghaddam Mahmood & Rongved, Pål (2008). Synthesis of cyclic peptide analogues of the 310 helical Pro138-Gly144 segment of human aquaporin-4 by olefin metathesis. Fulltekst i vitenarkiv
• Klaveness, Jo & Rongved, Pål (2008). Smør deg inn med Omega 3. [Journal]. NRK Nordland. Fulltekst i vitenarkiv
• Klaveness, Jo & Rongved, Pål (2008). Har knekt omega-3-koden. [Internet]. Forskning.no. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar (2006). Synthesis and 15-LO inhibitory activity of triazoles derived from Combretastatin A-4. Fulltekst i vitenarkiv 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.

• Rongved, Pål (2005). Forskningsbasert Innovasjon. Fulltekst i vitenarkiv
• Rongved, Pål (2005). Hva betyr det for de norske TTO-kontorene (Technology Transfer Office) at Norge ikke er med i EPO ? Fulltekst i vitenarkiv
• Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar (2005). Synthesis and biological activity of combretastatin derivatives. Fulltekst i vitenarkiv 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.

• Odlo, Kristin; Klaveness, Jo; Rongved, Pål & Hansen, Trond Vidar (2005). Synthesis of Combretastatin A-1 and B-1. Fulltekst i vitenarkiv 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.

• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv 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.

• 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. Fulltekst i vitenarkiv 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.

• Grøthe, Bendik Melling; Bonge-Hansen, Tore & Rongved, Pål (2015). Syntese av myxin og myxinderivater som potensielle legemidler mot akutt myelogen leukemi. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Langgård, Øyvind Bækkelund; Krengel, Ute; Rongved, Pål & Burschowsky, Daniel (2014). Purification of Liver X Receptors - "A slippery slope through half-charted territory". Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  Stadig flere lider av livsstilssykdommer som forkalkning av blodårene, diabetes og fedme. Disse lidelsene fører ofte med seg de to hovedårsakene for dødsfall blant menn og kvinner, nemlig hjerte- og karsykdommer, og kreft. Alle disse lidelsene og de dødelige sykdommene som følger med dem, kan før eller siden relateres til metabolisme, hvor tusenvis av proteiner og faktorer er involvert. Syklusene og interaksjonene innenfor metabolismen kan være svært komplekse, men bakom er genene som styrer alt. Lever X Reseptorer (LXR) er transkripsjonsfaktorer innenfor kjernereseptorfamilien. To isoformer av LXR har blitt identifisert, LXRα og LXRβ, med 78% likhet i proteinsekvensene i deres to ligand-bindingsdomener. Dyrestudier og in vivo studier har vist at manipulering av LXR ekspresjon har en effekt på de forventede sykdommene som aterosklerose, diabetes, inflammasjon, fedme, og overraskende nok også Alzheimers sykdom og visse typer kreft. De fleste ligander identifisert for LXR er endogene oksysteroler, noe som gjør LXR til ideelle farmasøytiske mål for medisiner mot metabolisme relaterte sykdommer. For strukturbasert drug design er det viktig å oppnå strukturer av de ligand-bindene domenene (LBD) i LXR med ligand. LBDene har blitt produsert, renset og krystallisert av flere grupper, men ingen strukturer av LXR LBD er løst der isoformene er bundet til samme endogene ligand. Målet med dette masterprosjektet var å rekombinant produsere, rense og krystallisere LXR LBD i kompleks med samme endogene og syntetiske ligander. Det var forventet at prosjektet skulle være ukomplisert, men det viste seg å ikke være tilfellet. Under produksjon av proteinene oppsto det mange problemer. De originale konstruktene gav lite eller ikke noe løselig protein under produksjon, men store mengder av protein i uløselige inklusjonslegemer. Vi forsøkte å variere kondisjonene og ha en ligand tilstedeværende i alle løsninger under ekspresjon, og transformere konstruktene inn i kuldetilpassede celler, men alle forsøk gav de samme resultatene med uløselig protein. Vi forsøkte dermed å rense protein fra inklusjonlegemene og folde proteinene in vitro. Dette resulterte i ustabile proteiner som ble utfelt ved konsentrering. Det proteinet renset fra den lille løselige fraksjonen ble brukt til krystalliseringsforsøk. Dette gav ingen krystaller, antageligvis på grunn av rensetag en som forsatt satt på proteinet. Rensetag en viste seg å være vanskelig å få av ettersom enterokinase er svært uspesifikk. Genene for LXR LBD ble klonet inn i en annen vektor som koder for periplasmisk ekspresjon.

Se alle arbeider i NVA