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  • 51. Bucar, Franz
    et al.
    Jachak, Sanjay M.
    Noreen, Ylva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Kartnig, Theodor
    Perera, Premila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Schubert-Zsilavecz, Manfred
    Amentoflavone from Biophytum sensitivum and its effect on COX-1/COX-2 catalysed prostaglandin biosynthesis1998Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 64, nr 4, s. 373-374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amentoflavone (13′, ll8-biapigenin) was isolated from the roots of Biophytum sensitivum DC. (Oxalidaceae) and proved to be a selective inhibitor of cyclooxygenase (COX)-1 catalysed prostaglandin biosynthesis when tested in vitro with an IC50 value of 12.4 µM (standard: indomethacin, IC50 = 1.1 µM). Doses of up to 37 µM showed only a slight inhibition in the corresponding COX-2 assay. Quantification of amentoflavone was carried out by reversed phase HPLC in methanolic and aqueous extracts of the roots, stems and leaves. Highest amounts of amentoflavone were detected in methanolic extracts of roots and stems (0.26-0.35%), while considerably lower amounts were detected in the corresponding water extracts.

  • 52.
    Buonfiglio, Rosa
    et al.
    AstraZeneca R&D, Chem Innovat Ctr, Discovery Sci, SE-43183 Molndal, Sweden..
    Engkvist, Ola
    AstraZeneca R&D, Chem Innovat Ctr, Discovery Sci, SE-43183 Molndal, Sweden..
    Varkonyi, Peter
    AstraZeneca R&D, Chem Innovat Ctr, Discovery Sci, SE-43183 Molndal, Sweden..
    Henz, Astrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Vikeved, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Kogej, Thierry
    AstraZeneca R&D, Chem Innovat Ctr, Discovery Sci, SE-43183 Molndal, Sweden..
    Investigating Pharmacological Similarity by Charting Chemical Space2015Ingår i: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 55, nr 11, s. 2375-2390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, biologically relevant areas of the chemical space were analyzed using ChemGPS-NP. This application enables comparing groups of ligands within a multidimensional space based on principle components derived from physicochemical descriptors. Also, 3D visualization of the ChemGPS-NP global map can be used to conveniently evaluate bioactive compound similarity and visually distinguish between different types or groups of compounds. To further establish ChemGPS-NP as a method to accurately represent the chemical space, a comparison with structure-based fingerprint has been performed. Interesting complementarities between the two descriptions of molecules were observed. It has been shown that the accuracy of describing molecules with physicochemical descriptors like in ChemGPS-NP is similar to the accuracy of structural fingerprints in retrieving bioactive molecules. Lastly, pharmacological similarity of structurally diverse compounds has been investigated in ChemGPS-NP space. These results further strengthen the case of using ChemGPS-NP as a tool to explore and visualize chemical space.

  • 53.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Distribution and Chemical Diversity of Cyclotides from Violaceae: Impact of Structure on Cytotoxic Activity and Membrane Interactions2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    During the last decade there has been increased interest in the cyclotide protein family, which consist of a circular chain of approximately 30 amino acids, including six cysteines that form three disulfide bonds, arranged in a cyclic cystine knot motif. This thesis gives new insights in cyclotide distribution and occurrence in the plant family Violaceae, structure-activity relationships for cytotoxic effects, membrane disruption and adsorption on lipid membranes, and evaluates toxicity and anti-tumor activity in vivo.

    A large-scale analysis was done on over 200 samples covering 17 of the 23 genera in Violaceae, and cyclotides were positively identified in almost 150 of approximately 900 known species. Conclusions are that the Violaceae is an extremely rich source of cyclotides, and that they are ubiquitous among all species in that plant family.

    After investigating the cyclotides' cytotoxicity it was evident that the effects were immediate and occurred at low micromolar concentrations. To understand the relationships between structure and activity, approximately 30 cyclotides and cyclotide derivates were assayed for cytotoxicity. Results showed that the overall charge is of minor influence on activity and revealed a strong correlation between an intact hydrophobic molecular surface and cytotoxic effect.

    The cytotoxic activity is mainly due to interactions between peptides and target membranes, illustrated by prototypic cyclotides' ability to induce liposome leakage and adsorb to lipid membranes. Cyclotides were strongly lytic against zwitterionic liposomes, less when cholesterol was included, while for anionic liposomes, activity depend on the net charge of cyclotide. A similar pattern was observed for the adsorption of the cyclotides to anionic bilayers, in which strong lytic activity was coupled with high adsorption.

    To further evaluate cyclotides cytotoxic effects, in vivo studies were conducted, both for acute toxicity and anti-tumor efficacy in mice. Two different methods were used: hollow fiber method and traditional xenografts, but no significant anti-tumor effects were detected. The results indicate that anti-tumor effects are minor or absent at tolerable doses and that cyclotides have a very abrupt in vivo toxicity profile, with lethality after single injection at 2.0 mg/kg.

    Delarbeten
    1. Cyclotide proteins and precursors from the genus Gloeospermum: filling a blank spot in the cyclotide map of Violaceae
    Öppna denna publikation i ny flik eller fönster >>Cyclotide proteins and precursors from the genus Gloeospermum: filling a blank spot in the cyclotide map of Violaceae
    Visa övriga...
    2010 (Engelska)Ingår i: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 71, nr 1, s. 13-20Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cyclotides are disulfide-rich plant proteins that are exceptional in their cyclic structure; their N and C termini are joined by a peptide bond, forming a continuous circular backbone, which is reinforced by three interlocked disulfide bonds. Cyclotides have been found mainly in the coffee (Rubiaceae) and violet (Violaceae) plant families. Within the Violaceae, cyclotides seem to be widely distributed, but the cyclotide complements of the vast majority of Violaceae species have not yet been explored. This study provides insight into cyclotide occurrence, diversity and biosynthesis in the Violaceae, by identifying mature cyclotide proteins, their precursors and enzymes putatively involved in their biosynthesis in the tribe Rinoreeae and the genus Gloeospermum. Twelve cyclotides from two Panamanian species, Gloeospermum pauciflorum Hekking and Gloeospermum blakeanum (Standl.) Hekking (designated Glopa A-E and Globa A-G, respectively) were characterised through cDNA screening and protein isolation. Screening of cDNA for the oxidative folding enzymes protein-disulfide isomerase (PDI) and thioredoxin (TRX) resulted in positive hits in both species. These enzymes have demonstrated roles in oxidative folding of cyclotides in Rubiaceae, and results presented here indicate that Violaceae plants have evolved similar mechanisms of cyclotide biosynthesis. We also describe PDI and TRX sequences from a third cyclotide-expressing Violaceae species, Viola biflora L., which further support this hypothesis.

    Nyckelord
    Cyclotide, cyclic peptide, Gloeospermum blakeanum, Gloeospermum pauciflorum, Violaceae, protein-disulfide isomerase, thioredoxin, precursor
    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-125029 (URN)10.1016/j.phytochem.2009.09.023 (DOI)000274374100002 ()19879608 (PubMedID)
    Tillgänglig från: 2010-05-07 Skapad: 2010-05-07 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    2. Distribution of cicular peptides in plants: Large scale mapping of cyclotides in the Violaceae
    Öppna denna publikation i ny flik eller fönster >>Distribution of cicular peptides in plants: Large scale mapping of cyclotides in the Violaceae
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    During last decade there has been increased interest in the small, cysteine-rich cyclotide proteins found in plant species of the violet family (Violaceae). These cyclotides consist of a circular chain of approximately 30 amino acids, including six cysteines that form three disulfide bonds, arranged in a cyclic cystine knot motif. In this study we map the occurrence and distribution of cyclotides in the Violaceae. Plant material was obtained from herbarium sheets containing samples up to 200 years old. Even the oldest specimens exhibited a remarkable stability of cyclotides in the preserved leaves, with no degradation products observable, making them one of the most stable proteins in nature. We analyzed the cyclotide content in over 200 samples covering 17 of the 23 genera, and positively identified cyclotides in almost 150 of approximately 900 known species in the Violaceae. Each species contained a unique set of between one and 25 cyclotides, of which many were exclusive to individual species. The estimated number of different cyclotides in the Violaceae is 5,000-25,000. We conclude that the Violaceae is an extremely rich source of cyclotides, and we propose that cyclotides are ubiquitous among all Violaceae species.

    Nyckelord
    Cyclotide, Violaceae
    Identifikatorer
    urn:nbn:se:uu:diva-131137 (URN)
    Tillgänglig från: 2010-09-27 Skapad: 2010-09-24 Senast uppdaterad: 2010-09-27
    3. Cytotoxic potency of small macrocyclic knot proteins: Structure-activity and mechanistic studies of native and chemically modified cyclotides
    Öppna denna publikation i ny flik eller fönster >>Cytotoxic potency of small macrocyclic knot proteins: Structure-activity and mechanistic studies of native and chemically modified cyclotides
    Visa övriga...
    2011 (Engelska)Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 11, s. 4306-4314Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The cyclotides are a family of circular and knotted proteins of natural origin with extreme enzymatic and thermal stability and active in a wide range of biological activities make them promising tools for pharmaceutical and crop-protection applications. The cyclotides are divided into two subfamilies depending on the presence (Möbius) or absence (bracelet) of a cis-Pro peptide bond. In the current work we report a series of experiments to give further insight into the structure activity relationship of cyclotides in general, and the differences between subfamilies and the role of their hydrophobic surface in particular. Selective chemical modifications of Glu, Arg, Lys and Trp residues was tested for cytotoxic activity and derivatives in which the Trp residue was modified showed low effect, suggesting the existence of a connection between hydrophobicity and activity. However, over the full set of cyclotides examined, there was no strong correlation between the cytotoxic activity and their hydrophobicity. Instead, it seems more like that the distribution of charged and hydrophobic residues determines the ultimate degree of potency. Furthermore, we found that while the Glu residue is very important in maintaining the activity of the bracelet cyclotide cycloviolacin O2, it is much less important in the Möbius cyclotides. However, despite these differences, a systematic test of mixtures of cyclotides, even from both subfamilies revealed that they act in an additive way.

     

    Nyckelord
    Cyclotide, Additive effects, Cytotoxicity
    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-131139 (URN)10.1039/c0ob00966k (DOI)000290735300043 ()21491023 (PubMedID)
    Tillgänglig från: 2010-09-27 Skapad: 2010-09-24 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    4. Mechanism of action of cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes
    Öppna denna publikation i ny flik eller fönster >>Mechanism of action of cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes
    Visa övriga...
    2007 (Engelska)Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 70, nr 4, s. 643-647Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In recent years, the cyclotides have emerged as the largest family of naturally cyclized proteins. Cyclotides display potent cytotoxic activity that varies with the structure of the proteins, and combined with their unique structure, they represent novel cytotoxic agents. However, their mechanism of action is yet unknown. In this work we show that disruption of cell membranes plays a crucial role in the cytotoxic effect of the cyclotide cycloviolacin O2 (1), which has been isolated from Viola odorata. Cell viability and morphology studies on the human lymphoma cell line U-937 GTB showed that cells exposed to 1 displayed disintegrated cell membranes within 5 min. Functional studies on calcein-loaded HeLa cells and on liposomes showed rapid concentration-dependent release of their respective internal contents. The present results show that cyclotides have specific membrane-disrupting activity.

    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-103776 (URN)10.1021/np070007v (DOI)000246007200028 ()17378610 (PubMedID)
    Tillgänglig från: 2009-05-20 Skapad: 2009-05-20 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    5. Evaluation of toxicity and anti-tumour activity of cycloviolacin O2 in mice.
    Öppna denna publikation i ny flik eller fönster >>Evaluation of toxicity and anti-tumour activity of cycloviolacin O2 in mice.
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    2010 (Engelska)Ingår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 94, nr 5, s. 626-634Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v. 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v. 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC50 values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2–3 days; lower doses were without complications.

    Nyckelord
    Cyclotides, toxicity, in vivo, xenograft, cycloviolacin O2
    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-131140 (URN)10.1002/bip.21408 (DOI)000282930400009 ()20564012 (PubMedID)
    Tillgänglig från: 2010-09-27 Skapad: 2010-09-24 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    6. Membrane integrity as a target for cyclotide cytotoxic activity
    Öppna denna publikation i ny flik eller fönster >>Membrane integrity as a target for cyclotide cytotoxic activity
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The cyclotides are a family of plant-derived proteins that occur in plants from the Violaceae (violet) and Rubiaceae (coffee) families and have a diverse range of biological activities, including cytotoxic, hemolytic, antimicrobial, and insecticidal activities; the latter suggests their natural function lies in plant defense. In the current study we have investigated the membrane-disrupting and adsorption ability of prototypic cyclotides and correlated these findings to their cytotoxic properties. We also included modifications of selected charged amino acids in cycloviolacin O2, previously shown to be of importance for its cytotoxic activity. The cyclotides’ cytotoxic activity, ability to adsorb and disrupt model lipid membranes of different charge densities was investigated, e.g. by fluorescence spectroscopy, ellipsometry, and circular dichroism. Cytotoxicity of the native cyclotides was demonstrated to correlate to membrane adsorption and lytic activity. Hence, the activity of native cyclotides is mainly due to interactions between the proteins and the phospholipids in the target membrane. Striking effects of single amino acid variations in cycloviolacin O2 on its membrane interaction were also demonstrated.

     

    Nyckelord
    Cyclotide, Cytotoxicity, Membrane, Adsorption
    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-131107 (URN)
    Tillgänglig från: 2010-09-27 Skapad: 2010-09-22 Senast uppdaterad: 2018-01-12
  • 54.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Goransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Mapping of small cysteine rich defense proteins in Violaceae: A novel suite of cyclotides from the genus Gloeospermum2008Konferensbidrag (Refereegranskat)
  • 55.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gruber, Christian W
    Rizzardi, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Herrmann, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Craik, David J
    Gupta, Mahabir P
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Cyclotide proteins and precursors from the genus Gloeospermum: filling a blank spot in the cyclotide map of Violaceae2010Ingår i: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 71, nr 1, s. 13-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are disulfide-rich plant proteins that are exceptional in their cyclic structure; their N and C termini are joined by a peptide bond, forming a continuous circular backbone, which is reinforced by three interlocked disulfide bonds. Cyclotides have been found mainly in the coffee (Rubiaceae) and violet (Violaceae) plant families. Within the Violaceae, cyclotides seem to be widely distributed, but the cyclotide complements of the vast majority of Violaceae species have not yet been explored. This study provides insight into cyclotide occurrence, diversity and biosynthesis in the Violaceae, by identifying mature cyclotide proteins, their precursors and enzymes putatively involved in their biosynthesis in the tribe Rinoreeae and the genus Gloeospermum. Twelve cyclotides from two Panamanian species, Gloeospermum pauciflorum Hekking and Gloeospermum blakeanum (Standl.) Hekking (designated Glopa A-E and Globa A-G, respectively) were characterised through cDNA screening and protein isolation. Screening of cDNA for the oxidative folding enzymes protein-disulfide isomerase (PDI) and thioredoxin (TRX) resulted in positive hits in both species. These enzymes have demonstrated roles in oxidative folding of cyclotides in Rubiaceae, and results presented here indicate that Violaceae plants have evolved similar mechanisms of cyclotide biosynthesis. We also describe PDI and TRX sequences from a third cyclotide-expressing Violaceae species, Viola biflora L., which further support this hypothesis.

  • 56.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Chemistry and Biology of Cyclotides: Circular Plant Peptides Outside the Box2014Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 77, nr 3, s. 724-736Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cyclotides stand out as the largest family of circular proteins of plant origin hitherto known, with more than 280 sequences isolated at peptide level and many more predicted from gene sequences. Their unusual stability resulting from the signature cyclic cystine knot (CCK) motif has triggered a broad interest in these molecules for potential therapeutic and agricultural applications. Since the time of the first cyclotide discovery, our laboratory in Uppsala has been engaged in cyclotide discovery as well as the development of protocols to isolate and characterize these seamless peptides. We have also developed methods to chemically synthesize cyclotides by Fmoc-SPPS, which are useful in protein grafting applications. In this review, experience in cyclotide research over two decades and the recent literature related to their structures, synthesis, and folding as well the recent proof-of-concept findings on their use as "epitope" stabilizing scaffolds are summarized.

  • 57.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Herrmann, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Tran, Rosetti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Kivelä, Jan-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lomize, Andrei
    University of Michigan, Little College of Pharmacy.
    Gullbo, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Cytotoxic potency of small macrocyclic knot proteins: Structure-activity and mechanistic studies of native and chemically modified cyclotides2011Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 11, s. 4306-4314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cyclotides are a family of circular and knotted proteins of natural origin with extreme enzymatic and thermal stability and active in a wide range of biological activities make them promising tools for pharmaceutical and crop-protection applications. The cyclotides are divided into two subfamilies depending on the presence (Möbius) or absence (bracelet) of a cis-Pro peptide bond. In the current work we report a series of experiments to give further insight into the structure activity relationship of cyclotides in general, and the differences between subfamilies and the role of their hydrophobic surface in particular. Selective chemical modifications of Glu, Arg, Lys and Trp residues was tested for cytotoxic activity and derivatives in which the Trp residue was modified showed low effect, suggesting the existence of a connection between hydrophobicity and activity. However, over the full set of cyclotides examined, there was no strong correlation between the cytotoxic activity and their hydrophobicity. Instead, it seems more like that the distribution of charged and hydrophobic residues determines the ultimate degree of potency. Furthermore, we found that while the Glu residue is very important in maintaining the activity of the bracelet cyclotide cycloviolacin O2, it is much less important in the Möbius cyclotides. However, despite these differences, a systematic test of mixtures of cyclotides, even from both subfamilies revealed that they act in an additive way.

     

  • 58.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Larsson, Sonny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Yeshak, Mariamawit
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Rosengren, Johan
    University of Queensland, Institute for Molecular Bioscience.
    Craik, David
    University of Queensland, Institute for Molecular Bioscience.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Distribution of cicular peptides in plants: Large scale mapping of cyclotides in the ViolaceaeManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    During last decade there has been increased interest in the small, cysteine-rich cyclotide proteins found in plant species of the violet family (Violaceae). These cyclotides consist of a circular chain of approximately 30 amino acids, including six cysteines that form three disulfide bonds, arranged in a cyclic cystine knot motif. In this study we map the occurrence and distribution of cyclotides in the Violaceae. Plant material was obtained from herbarium sheets containing samples up to 200 years old. Even the oldest specimens exhibited a remarkable stability of cyclotides in the preserved leaves, with no degradation products observable, making them one of the most stable proteins in nature. We analyzed the cyclotide content in over 200 samples covering 17 of the 23 genera, and positively identified cyclotides in almost 150 of approximately 900 known species in the Violaceae. Each species contained a unique set of between one and 25 cyclotides, of which many were exclusive to individual species. The estimated number of different cyclotides in the Violaceae is 5,000-25,000. We conclude that the Violaceae is an extremely rich source of cyclotides, and we propose that cyclotides are ubiquitous among all Violaceae species.

  • 59.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Cyclotide-membrane interactions: defining factors of membrane binding, depletion and disruption2011Ingår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1808, nr 11, s. 2665-2673Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cyclotide family of plant-derived peptides is defined by a cyclic backbone and three disulfide bonds locked into a cyclic cystine knot. They display a diverse range of biological activities, many of which have been linked to an ability to target biological membranes. In the current work, we show that membrane binding and disrupting properties of prototypic cyclotides are dependent on lipid composition, using neutral (zwitterionic) membranes with or without cholesterol and/or anionic lipids. Cycloviolacin O2 (cyO2) caused potent membrane disruption, and showed selectivity towards anionic membranes, whereas kalata B1 and kalata B2 cyclotides were significantly less lytic towards all tested model membranes. To investigate the role of the charged amino acids of cyO2 in the membrane selectivity, these were neutralized using chemical modifications. In contrast to previous studies on the cytotoxic and antimicrobial effects of these derivatives, the Glu6 methyl ester of cyO2 was more potent than the native peptide. However, using membranes of Escherichia coil lipids gave the opposite result: the activity of the native peptide increased 50-fold. By using a combination of ellipsometry and LC-MS, we demonstrated that this unusual membrane specificity is due to native cyO2 extracting preferentially phosphatidylethanolamine-lipids from the membrane, i.e., PE-C16:0/cyC17:0 and PE-C16:0/C18:1.

  • 60.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Membrane integrity as a target for cyclotide cytotoxic activityManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The cyclotides are a family of plant-derived proteins that occur in plants from the Violaceae (violet) and Rubiaceae (coffee) families and have a diverse range of biological activities, including cytotoxic, hemolytic, antimicrobial, and insecticidal activities; the latter suggests their natural function lies in plant defense. In the current study we have investigated the membrane-disrupting and adsorption ability of prototypic cyclotides and correlated these findings to their cytotoxic properties. We also included modifications of selected charged amino acids in cycloviolacin O2, previously shown to be of importance for its cytotoxic activity. The cyclotides’ cytotoxic activity, ability to adsorb and disrupt model lipid membranes of different charge densities was investigated, e.g. by fluorescence spectroscopy, ellipsometry, and circular dichroism. Cytotoxicity of the native cyclotides was demonstrated to correlate to membrane adsorption and lytic activity. Hence, the activity of native cyclotides is mainly due to interactions between the proteins and the phospholipids in the target membrane. Striking effects of single amino acid variations in cycloviolacin O2 on its membrane interaction were also demonstrated.

     

  • 61.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Svedlund, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Felth, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Hassan, Saadia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Herrmann, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Clark, Richard J.
    University of Queensland, Institute for Molecular Bioscience.
    Craik, David J.
    University of Queensland, Institute for Molecular Bioscience.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Claeson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gullbo, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Evaluation of toxicity and anti-tumour activity of cycloviolacin O2 in mice.2010Ingår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 94, nr 5, s. 626-634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v. 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v. 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC50 values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2–3 days; lower doses were without complications.

  • 62.
    Burman, Robert
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Yeshak, Mariamawit Y.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Univ Addis Ababa, Sch Pharm, Dept Pharmacognosy, Addis Ababa, Ethiopia..
    Larsson, Sonny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Craik, David J.
    Univ Queensland, Inst Mol Biosci, Chem & Struct Biol Div, Craik Lab, Brisbane, Qld, Australia..
    Rosengren, K. Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Univ Queensland, Sch Biomed Sci, Lab Peptide Struct Biol, Brisbane, Qld, Australia..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Distribution of circular proteins in plants: large-scale mapping of cyclotides in the Violaceae2015Ingår i: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 6, artikel-id 855Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During the last decade there has been increasing interest in small circular proteins found in plants of the violet family (Violaceae). These so-called cyclotides consist of a circular chain of approximately 30 amino acids, including six cysteines forming three disulfide bonds, arranged in a cyclic cystine knot (CCK) motif. In this study we map the occurrence and distribution of cyclotides throughout the Violaceae. Plant material was obtained from herbarium sheets containing samples up to 200 years of age. Even the oldest specimens contained cyclotides in the preserved leaves, with no degradation products observable, confirming their place as one of the most stable proteins in nature. Over 200 samples covering 17 of the 23-31 genera in Violaceae were analyzed, and cyclotides were positively identified in 150 species. Each species contained a unique set of between one and 25 cyclotides, with many exclusive to individual plant species. We estimate the number of different cyclotides in the Violaceae to be 5000-25,000, and propose that cyclotides are ubiquitous among all Violaceae species. Twelve new cyclotides from six phylogenetically dispersed genera were sequenced. Furthermore, the first glycosylated derivatives of cyclotides were identified and characterized, further increasing the diversity and complexity of this unique protein family.

  • 63.
    Carella, Mirco
    et al.
    CSIC, CEAB, Acces Cala St Francesc 14, Blanes 17300, Girona, Spain..
    Agell, Gemma
    CSIC, CEAB, Acces Cala St Francesc 14, Blanes 17300, Girona, Spain..
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Museum Natl Hist Nat, Dept Milieux & Peuplements Aquat, UMR BOrEA 7208, Paris, France..
    Uriz, Maria J.
    CSIC, CEAB, Acces Cala St Francesc 14, Blanes 17300, Girona, Spain..
    Phylogenetic Reassessment of Antarctic Tetillidae (Demospongiae, Tetractinellida) Reveals New Genera and Genetic Similarity among Morphologically Distinct Species2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 8, artikel-id e0160718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Species of Tetillidae are distributed worldwide. However, some genera are unresolved and only a few genera and species of this family have been described from the Antarctic. The incorporation of 25 new COI and 18S sequences of Antarctic Tetillidae to those used recently for assessing the genera phylogeny, has allowed us to improve the resolution of some poorly resolved nodes and to confirm the monophyly of previously identified clades. Classical genera such as Craniella recovered their traditional diagnosis by moving the Antarctic Tetilla from Craniella, where they were placed in the previous family phylogeny, to Antarctotetilla gen. nov. The morphological re-examination of specimens used in the previous phylogeny and their comparison to the type material revealed misidentifications. The proposed monotypic new genus Levantinella had uncertain phylogenetic relationships depending on the gene partition used. Two more clades would require the inclusion of additional species to be formally established as new genera. The parsimony tree based on morphological characters and the secondary structure of the 18S (V4 region) almost completely matched the COI M1-M6 and the COI+18S concatenated phylogenies. Morphological synapomorphies have been identified for the genera proposed. New 15 28S (D3-D5) and 11 COI I3-M11 partitions were exclusively sequenced for the Antarctic species subset. Remarkably, species within the Antarctic genera Cinachyra (C. barbata and C. antarctica) and Antarctotetilla (A. leptoderma, A. grandis, and A. sagitta), which are clearly distinguishable morphologically, were not genetically differentiated with any of the markers assayed. Thus, as it has been reported for other Antarctic sponges, both the mitochondrial and nuclear partitions used did not differentiate species that were well characterized morphologically. Antarctic Tetillidae offers a rare example of genetically cryptic (with the traditional markers used for sponges), morphologically distinct species.

  • 64.
    Carstens, Bodil B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia..
    Rosengren, K. Johan
    Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia..
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Schempp, Stefanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Dahlstrom, Mia
    SP Tech Res Inst Sweden, Dept Chem Mat & Surfaces, SE-41346 Gothenburg, Sweden..
    Clark, Richard J.
    Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Isolation, Characterization, and Synthesis of the Barrettides: Disulfide-Containing Peptides from the Marine Sponge Geodia barretti2015Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 78, nr 8, s. 1886-1893Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two disulfide-containing peptides, barrettides A (1) and B (2), from the cold-water marine sponge Geodia barretti are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of 1 was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of 1 revealed that these peptides possess a unique fold consisting of a long beta-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either Escherichia coli or Staphylococcus aureus but displayed antifouling activity against barnacle larvae (Balanus improvisus) without lethal effects in the concentrations tested.

  • 65.
    Claeson, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Some aspects of bioassay methods in natural-product research aimed at drugl ead discovery1997Ingår i: Trends in Biotechnology, ISSN 0167-7799, E-ISSN 1879-3096, Vol. 15, nr 7, s. 245-248Artikel i tidskrift (Refereegranskat)
  • 66.
    Claeson, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Johansson, Senia
    Luijendijk, Teus
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Fractionation protocol for the isolation of polypeptides from plant biomass1998Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 61, nr 1, s. 77-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A fractionation protocol for the isolation of a highly purified polypeptide fraction from plant biomass is described. The procedure dereplicates ubiquitous substance classes known to interfere with bioassays often used in natural product-based drug discovery programs. The protocol involves pre-extraction with dichloromethane, extraction with ethanol (50%), removal of tannins with polyamide, removal of low-molecular-weight components with size-exclusion chromatography over Sephadex G-10, and final removal of salts and polysaccharides with solid-phase extraction using reversed-phase cartridges. The method has been applied to the aerial parts of Viola arvensis, resulting in the isolation of a peptide fraction that on further separation yielded a novel 29-residue macrocyclic polypeptide named varv peptide A, cyclo(-TCVGGTCNTPGCSCSWPVCTRNGLPVCGE-).

  • 67.
    Claeson, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Johansson, Senia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Luijendijk, Teus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Fractionation protocol for the isolation of polypeptides from plant biomass1998Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 61, nr 1, s. 77-81Artikel i tidskrift (Refereegranskat)
  • 68.
    Claeson, Ubonwan Pongprayoon
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Malmfors, Torbjörn
    Wikman, Georg
    Bruhn, Jan G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Adhatoda vasica: a critical review of ethnopharmacological and toxicological data2000Ingår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 72, nr 1-2, s. 1-20Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Adhatoda vasica (L.) Nees is a well-known plant drug in Ayurvedic and Unani medicine. It has been used for the treatment of various diseases and disorders, particularly for the respiratory tract ailments. During the last 20 years, several scientific reports on oxytocic and abortifacient effects of vasicine and alkaloid derived from the plant have appeared. This leads to questions concerning the safety of A. vasica as a herbal medicine. In this article, the major data on traditional uses as well as ethnopharmacological and toxicological studies, both published and unpublished, are reviewed and commented upon. The data have been evaluated from the point of view of correctness, reliability, relevance and importance for the overall evaluation of the safety of A. vasica.

  • 69.
    Craik, David J.
    et al.
    Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, Brisbane, Qld 4072, Australia..
    Shim, Youn Young
    Univ Saskatchewan, Coll Agr & Bioresources, Dept Plant Sci, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada.;Prairie Tide Chem Inc, 102 Melville St, Saskatoon, SK S7J 0R1 5A8, Canada.;Jinan Univ, Dept Food Sci & Engn, Guangdong Saskatchewan Oilseed Joint Lab, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Moss, Gerard P.
    Queen Mary Univ London, Sch Biol & Chem Sci, Mile End Rd, London E1 4NS, England..
    Tan, Ninghua
    China Pharmaceut Univ, Sch Tradit Chinese Med, 639 Longmian Ave, Nanjing 211198, Jiangsu, Peoples R China..
    Jadhav, Pramodkumar D.
    Univ Saskatchewan, Coll Agr & Bioresources, Dept Plant Sci, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada..
    Shen, Jianheng
    Univ Saskatchewan, Coll Agr & Bioresources, Dept Plant Sci, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada..
    Reaney, Martin J. T.
    Univ Saskatchewan, Coll Agr & Bioresources, Dept Plant Sci, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada.;Prairie Tide Chem Inc, 102 Melville St, Saskatoon, SK S7J 0R1 5A8, Canada.;Jinan Univ, Dept Food Sci & Engn, Guangdong Saskatchewan Oilseed Joint Lab, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China..
    Nomenclature of homodetic cyclic peptides produced from ribosomal precursors: An IUPAC task group interim report2016Ingår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 106, nr 6, s. 917-924Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In 2015, an International Union of Pure and Applied Chemistry (IUPAC) Task Group was formed to develop nomenclature recommendations for homodetic cyclic peptides produced from ribosomal precursors. Delegates of the 2015 International Conference on Circular Proteins (ICCP) were presented with the strengths and weaknesses of four published approaches to homodetic cyclic peptide nomenclature, and a summary of the ensuing discussion is presented here. This interim report presents a potentially novel suggestion-the use of Cahn-Ingold-Prelog rules to specify amino acid priority in homodetic peptides for consistent numbering. Indeed, this might be the first extension of the Cahn-Ingold-Prelog rules in five decades. The authors invite interested parties to contact the corresponding author with suggestions for the improvement of the proposed nomenclature; these ideas will be discussed and considered for inclusion in the final report.

  • 70. Cui, J.
    et al.
    Eneroth, P.
    Bruhn, J. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gynostemma pentaphyllum: identification of major sapogenins and differentiation from Panax species1999Ingår i: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 8, nr 3, s. 187-191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Four main dammarane-type aglycones of gypenosides, extracted from the aerial parts of Gynostemma pentaphyllum were identified by gas chromatography-mass spectrometry. By detecting these aglycones as well as the aglycones of ginsenosides, a difference in sapogenin composition between Gynostemma pentaphyllum and Panax species was observed, which can be used in the differentiation of these plant drugs.

  • 71. Cui, Jian-Fang
    et al.
    Eneroth, Peter
    Bruhn, Jan G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Arihara, Shigenobu
    Yoshikawa, Kazuko
    Alkaline cleavage of gypenosides and characterization of dammarane-type aglycones by gas chromatography mass spectrometry1998Ingår i: Phytochemical Analysis, ISSN 0958-0344, E-ISSN 1099-1565, Vol. 9, nr 3, s. 128-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Five dammarane-type aglycones, released from gypenosides following an alkaline cleavage procedure previously developed for ginsenosides, were separated and characterized by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation. A satisfactory identification among isomers of 20(S)-protopanaxadiol or 20(S)-protopanaxatriol was obtained.

  • 72.
    Cárdenas, Paco
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Thollesson, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    A new Hymedesmia (Demospongiae, Poecilosclerida) with large sigmas off western Sweden2016Ingår i: Journal of the Marine Biological Association of the United Kingdom, ISSN 0025-3154, E-ISSN 1469-7769, Vol. 96, nr 6, s. 1305-1312Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hymedesmia (Hymedesmia) lindstroemae sp. nov. collected at 178–210 m depth off the western Swedish coast is described. This encrusting sponge is notably characterized by its unusually large sigmas. This new species brings the number of Hymedesmia (Hymedesmia) species in Swedish waters to 30. A key for all the North Atlantic Hymedesmia (Hymedesmia) species with sigmas (32 species) is included.

  • 73. Dahlström, Mia
    et al.
    Lindgren, Fredrik
    Berntsson, Kent
    Sjögren, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Mårtensson, Lena G E
    Jonsson, Per R
    Elwing, Hans
    Evidence for different pharmacological targets for imidazoline compounds inhibiting settlement of the barnacle Balanus improvisus2005Ingår i: Journal of Experimental Zoology, ISSN 0022-104X, E-ISSN 1097-010X, Vol. 303A, nr 7, s. 551-562Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe the effect of eight different imidazoline/guanidinium compounds on the settlement and metamorphosis of larvae of the barnacle Balanus improvisus. These agents were chosen on the basis of their similar pharmacological classification in vertebrates and their chemical similarity to medetomidine and clonidine, previously described as highly potent settlement inhibitors (nanomolar range). Seven of the tested compounds were found to inhibit settlement in a dose-dependent manner in concentrations ranging from 100 nM to 10 microM without any significant lethal effects. In vertebrate systems these substances have overlapping functions and interact with both alpha-adrenoceptors as well as imidazoline binding sites. Antagonizing experiments using the highly specific alpha(2)-antagonist methoxy-idazoxan or agmatine (the putative endogenous ligand at imidazoline receptors) were performed to discriminate between putative pharmacological mechanisms involved in the inhibition of cyprid settlement. Agmatine was not able to reverse the effect of any of the tested compounds. However, methoxy-idazoxan almost completely abolished the settlement inhibition mediated by guanabenz (alpha(2)-agonist, I(2) ligand), moxonidine (alpha(2)-agonist, I(1) ligand) and tetrahydrozoline (alpha-agonist, I(2) ligand). The actions of cirazoline (alpha(1)-agonist, I(2) ligand) BU 224 (I(2) ligand) and metrazoline (I(2) ligand) were not reversed by treatment with methoxy-idazoxan. These results suggest that the settlement inhibition evoked by the I(2) ligands and alpha(2)-agonists used in this study of the neurologically simple but well-organized barnacle larva is mediated through different physiological targets important in the overall settlement process.

  • 74. Dahlström, Mia
    et al.
    Sjögren, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Jonsson, Per R.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lindh, Liselott
    Arnebrant, Thomas
    Pinori, Emiliano
    Elwing, Hans
    Berglin, Mattias
    Affinity states of biocides determine bioavailability and release rates in marine paints2015Ingår i: Biofouling (Print), ISSN 0892-7014, E-ISSN 1029-2454, Vol. 31, nr 2, s. 201-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A challenge for the next generation marine antifouling (AF) paints is to deliver minimum amounts of biocides to the environment. The candidate AF compound medetomidine is here shown to be released at very low concentrations, ie ng ml(-1) day(-1). Moreover, the release rate of medetomidine differs substantially depending on the formulation of the paint, while inhibition of barnacle settlement is independent of release to the ambient water, ie the paint with the lowest release rate was the most effective in impeding barnacle colonisation. This highlights the critical role of chemical interactions between biocide, paint carrier and the solid/aqueous interface for release rate and AF performance. The results are discussed in the light of differential affinity states of the biocide, predicting AF activity in terms of a high surface affinity and preserved bioavailability. This may offer a general framework for the design of low-release paint systems using biocides for protection against biofouling on marine surfaces.

  • 75.
    Demma, Jemal
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Engidawork, Ephrem
    Aboye, Teshome Leta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Hellman, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    An in vitro Study on the DNA Damaging Effects of Phytochemicals Partially Isolated from an Extract of Glinus lotoides2013Ingår i: Phytotherapy Research, ISSN 0951-418X, E-ISSN 1099-1573, Vol. 27, nr 4, s. 507-514Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An extract of Glinus lotoides, a medicinal plant used in Africa and Asia for various therapeutic purposes, was recently shown to cause DNA damage in vitro. To further explore the potential genotoxicity of this plant, fractionation of the crude extract was performed using reverse phase solid-phase extraction and a stepwise gradient elution of methanol in water. Four fractions were collected and subsequently analysed for their DNA damaging effects in mouse lymphoma cells using an alkaline version of the comet assay. To identify potential genotoxic and non-genotoxic principles, each fraction was then subjected to liquid chromatography coupled to mass spectrometry, LC-MS/MS. 1D and 2D nuclear magnetic resonance analyses were used to confirm the identity of some saponins. Although fractions containing a mixture of flavonoids and oleanane-type saponins or oleanane-type saponins alone produced no DNA damage, those containing hopane-type saponins exhibited a pronounced DNA damaging effect without affecting the viability of the cells. To conclude, even if this study presents evidence that hopane-type of saponins are endowed with a DNA damaging ability, further studies are needed before individual saponins can be cited as a culprit for the previously reported genotoxicity of the crude extract of G. lotoides.

  • 76.
    Ekenäs, Catarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Heidari, Nahid
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Andreasen, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Arnica (Asteraceae) phylogeny revisited using RPB2: Complex patterns and multiple d-paralogues2012Ingår i: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 64, nr 2, s. 261-270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The region coding for the second largest subunit of RNA polymerase II (RPB2) was explored for resolving interspecific relationships in Arnica and lower level taxa in general. The region between exons 17 and 23 was cloned and sequenced for 33 accessions of Arnica and four outgroup taxa. Three paralogues of the RPB2-d copy (RPB2-dA, B and C) were detected in Arnica and outgroup taxa, indicating that the duplications must have occurred before the divergence of Arnica. Parsimony and Bayesian analyses of separate alignments of the three copies reveal complex patterns in Arnica, likely reflecting a history of lineage sorting in combination with apomixis, polyploidization, and possibly hybridization. Cloned sequences of some taxa do not form monophyletic clades within paralogues, but form multiple strongly supported clades with sequences of other taxa. Some well supported groups are present in more than one paralogue and many groups are in line with earlier hypotheses regarding interspecific relationships within the genus. Low levels of homoplasy in combination with relatively high sequence variation indicates that the introns of the RPB2 region could be suitable for phylogenetic studies in low level taxonomy.

  • 77.
    Ekenäs, Catarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Systematisk botanik.
    Rosén, Josefin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Wagner, Steffen
    Albert-Ludwigs-Universität, Freiburg, Germany.
    Merfort, Irmgard
    Albert-Ludwigs-Universität, Freiburg, Germany.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Andreasen, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Systematisk botanik.
    Secondary chemistry and ribosomal DNA data congruencies in Arnica (Asteraceae)2009Ingår i: Cladistics, ISSN 0748-3007, E-ISSN 1096-0031, Vol. 25, nr 1, s. 78-92Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To investigate possible congruencies between DNA sequence data and secondary chemistry, we compared nuclear ribosomal DNA (nrDNA) sequence data, sesquiterpene lactone (STL) contents, and cytometric data from 35 accessions of 16 Arnica (Asteraceae) species and two outgroup taxa (Layia hieracioides and Madia sativa), using phylogenetic inference and principal component analysis (PCA). Several groups supporting multiple accessions of the same species (of A. montana, A. longifolia, A. gracilis, and A. chamissonis) are congruent between the phylogenetic trees based on nrDNA and STL data. Sesquiterpene lactone profiles were found to be highly consistent within multiple samples of A. montana and A. longifolia respectively. Moreover, sesquiterpene lactone data support subspecies classifications of A. chamissonis and A. parryi, with additional support from DNA sequence data and cytometric data. Morphology, STL data (PCA), cytometric data and DNA sequence data suggest a hybrid origin of one accession (A. gracilis × longifolia). In A. gracilis, A. latifolia, and Layia hieracioides, previously not investigated for STLs, we found large amounts of xanthalongin derivatives. This is the first time STLs have been reported from subtribe Madiinae.

  • 78.
    Ekenäs, Catarina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk biologi.
    Zebrowska, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Schuler, Barbara
    Vrede, Tobias
    Department of Ecology and Environmental Science, Umeå University, Sweden .
    Andreasen, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk biologi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Merfort, Irmgard
    Albert-Ludwigs- Universität, Freiburg, Germany.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Screening for Anti-Inflammatory Activity of 12 Arnica (Asteraceae) Species Assessed by Inhibition of NF-κB and Release of Human Neutrophil Elastase2008Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 74, nr 15, s. 1789-1794Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several species in the genus Arnica have been used in traditional medicine to treat inflammatory-related disorders. Extracts of twelve Arnica species and two species closely related to Arnica (Layia hieracioides and Madia sativa) were investigated for inhibition of human neutrophil elastase release and inhibition of transcription factor NF-κB. Statistical analyses reveal significant differences in inhibitory capacities between extracts. Sesquiterpene lactones of the helenanolide type, of which some are known inhibitors of human neutrophil elastase release and NF-κB, are present in large amounts in the very active extracts of A. montana and A. chamissonis. Furthermore, A. longifolia, which has previously not been investigated, shows a high activity similar to that of A. montana and A. chamissonis in both bioassays. Sesquiterpene lactones of the xanthalongin type are present in large amounts in A. longifolia and other active extracts and would be interesting to evaluate further.

  • 79.
    El-Kemary, Maged
    et al.
    Kafrelsheikh Univ, Div Photo & Nanochem, Dept Chem, Fac Sci, Kafr Al Sheikh 33516, Egypt..
    Ibrahim, Eslam
    Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt..
    A-Ajmi, Mohammad F.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, POB 2457, Riyadh 11451, Saudi Arabia..
    Khalifa, Shaden A. M.
    Karolinska Univ Hosp, Dept Expt Hematol, SE-14186 Stockholm, Sweden.;Stockholm Univ, Dept Mol Biosci, Wenner Gren Inst, SE-10691 Stockholm, Sweden..
    Alanazi, A. D.
    Shaqra Univ, Coll Appl Med Sci, KSA, POB 1678, Aldawadmi 11911, Saudi Arabia..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.;Uppsala Univ, Div Pharmacognosy, Dept Med Chem, Box 574, SE-75123 Uppsala, Sweden.;Univ Malaya, Dept Chem, Fac Sci, Kuala Lumpur 50603, Malaysia..
    Calendula officinalis-mediated biosynthesis of Silver Nanoparticles and their Electrochemical and Optical Characterization2016Ingår i: International Journal of Electrochemical Science, ISSN 1452-3981, E-ISSN 1452-3981, Vol. 11, nr 12, s. 10795-10805Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The metal nanoparticles synthesis is highly explored field of nanotechnology. The biological methods seem to be more effective. A simple and elegant method is adopted to prepare Silver nanoparticles (AgNPs) in a single step using Calendula officinalis extract (COE) as reducing and stabilizing agent. The plant extract is mixed with AgNO3 to get biosynthesized AgNPs. The biosynthesized AgNPs were both optically and electrochemically characterized by UV-Vis, Infrared spectroscopy, Transmission Electron Microscopy, Fluorescence spectroscopy, Zeta potential and Cyclic Voltammetry. The results showed Calendula officinalis extract is a useful bioreductant for the synthesis of AgNPs. This study infers that the size of biosynthesized AgNPs ranges from 30 to 50 nm. The surface plasmon resonance peak in the UV-Vis absorption spectra shows maximum absorption at 435 nm. Fluorescence spectra of silver nanoparticles, which show an emission peak at 468 nm have also been studied. Zeta potential analysis ensured the biosynthesized AgNPs are highly stable. Using this environmentally friendly method of biological AgNPs production supplies rates of biosynthesis facile in comparison with other chemical and engineered routes. The employment of traditional medicine in biosynthesis protocols can potentially open new doors in various human health and well-being implications such as cosmetics, foods and medicine.

  • 80.
    El-Kemary, Maged
    et al.
    Kafrelsheikh Univ, Div Photo & Nanochem, Dept Chem, Fac Sci, Kafr Al Sheikh 33516, Egypt..
    Zahran, Moustafa
    Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt..
    Khalifa, Shaden A. M.
    Karolinska Univ Hosp, Dept Expt Hematol, SE-14186 Stockholm, Sweden.;Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Univ Malaya, Dept Chem, Fac Sci, Kuala Lumpur 50603, Malaysia.;KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, Ecol Chem Grp, Stockholm, Sweden..
    Spectral characterisation of the silver nanoparticles biosynthesised using Ambrosia maritima plant2016Ingår i: Micro & Nano Letters, ISSN 1750-0443, E-ISSN 1750-0443, Vol. 11, nr 6, s. 311-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Silver nanoparticles (AgNPs) were biosynthesised by reducing silver nitrate (AgNO3) using Ambrosia maritima aqueous leaves extract. The biosynthesised AgNPs were characterised by transmission electron microscope, Fourier transform infrared spectroscopy and zeta potential analyser. The nanoparticles were generally found to be spherical in shape with average size of 30 nm and were stable at zeta potential of -26.29 mV. The data collected by cyclic voltammetry, ultraviolet-visible (UV-Vis) spectrophotometer and spectrofluorophotometer proved the characteristic electrochemical and optical properties of the biosynthesised AgNPs. The metallic nanoparticles showed an anodic peak at 0.4 mV, a surface plasmon resonance peak at 437 nm and a fluorescence emission peak at the wavelength of 467 nm. In conclusion, AgNPs biosynthesised using A. maritima proved to be compatible and feasible to be studied further in in vitro and in vivo systems. Overall, the biosynthesised AgNPs can be used as a tool applied in a broad range of industrial and medical applications.

  • 81.
    El-Seedi, H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Zahra, M A
    Göransson, U
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Verpoorte, R
    Cyclopeptide alkaloids2007Ingår i: Phytochemistry Reviews, ISSN 1568-7767, E-ISSN 1572-980X, Vol. 6, nr 1, s. 143-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this review, we discuss cyclopeptide alkaloids, their plant origin, and the way of separation, spectral analysis done for structure elucidation, stereochemistry, and their biological activities. In addition, we discuss briefly the chemosystematic significance of the cyclopeptide alkaloids based on their discovery in the family Olacaceae.

  • 82.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    New long-chained feruloyl ester from the bark of Cedrelinga catenaeformis2007Ingår i: Chemistry of Natural Compounds, ISSN 0009-3130, E-ISSN 1573-8388, Vol. 43, nr 3, s. 256-258Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tetradecyl ferulate and a new n-alkyl ester of 3-hydroxy-4-methoxy-trans-cinnamate (hexacosanylisoferulate) have been isolated from Cedrelinga catenaeformis Duke (Leguminoseae). The structures were determined by 1D- and 2D-NMR spectroscopy, mass spectrometry, chemical transformations and finally from unambiguous synthesis. This is the first report of long chained cinnamic acid ester derivative from the genus.

  • 83.
    El-Seedi, Hesham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    El-Said, A. M. A.
    Khalifa, S. A. M.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Borg-Karlson, A. -K
    Verpoorte, R.
    Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids2012Ingår i: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 60, nr 44, s. 10877-10895Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa, and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake, and pharmacokinetic properties.

  • 84.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Antimicrobial arylcoumarins from Asphodelus microcarpus2007Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 70, nr 1, s. 118-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A new aryl coumarin glucoside, asphodelin A 4'-O-beta-d-glucoside (1), and its aglycon, asphodelin A (2), were isolated from Asphodelus microcarpus. The structures were determined by detailed spectroscopic analysis and chemical transformation as 3-(2'-hydroxy-p-O-beta-d-glucopyranosyloxyphenyl)-4,7-dihydroxy-2H-1-benzopyran-2-one (1) and 3-(2',4'-dihydroxyphenyl)-4,7-dihydroxy-2H-1-benzopyran-2-one (2), respectively. These compounds were isolated following bioactivity-directed fractionation, using antimicrobial activity, in which 1 and 2 exhibited moderate and potent activities, respectively. This is the first report of a 3-arylcoumarin derivative, a rare class of isoflavonoids, from a plant in the family Liliaceae.

  • 85.
    El-Seedi, Hesham R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.