uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
1234567 151 - 200 av 321
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 151.
    Jacobsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Studies on cysteine-rich peptides from Nemertea and Violaceae: Proteomic and transcriptomic discovery and characterization2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The overall aims of the projects included in this thesis were to discover, synthesize and characterize disulphide-stabilized peptides from marine worms (Nemertea sp.) and plants (Viola sp.). 

    One of the main outcomes of this thesis is the discovery of a new family of highly active cysteine-rich toxins, alpha nemertides, from nemertean worms (paper II). Functional characterization and production routes of nemertides were further explored (papers II-III). In addition, 12 new cyclotides from the bog violet were discovered (paper I). Finally, transcriptomes and mucus of the Antarctic nemertean Parborlasia corrugatus were investigated for toxin content (paper IV).

     In paper I wild-type leaf and callus tissue of the endangered bog violet, V. uliginosa, were analyzed using transcriptomics and LC-MS, resulting in the discovery of 12 new cyclotides (i.e. cysteine-rich cyclic peptides). In addition, cyclotide expression under different cell-growth conditions was monitored.

    In paper II  the discovery and initial characterization of a new family of highly active peptides, the alpha nemertides, from the epidermal mucus of the world’s longest animal; Lineus longissimus is described. The most abundant alpha nemertide, alpha-1, was extracted in minute amounts, prompting the use solid phase peptide synthesis (SPPS) for further characterization. The tertiary structure of alpha-1 was elucidated and revealed an inhibitory cystine knot (ICK) framework. The knotted core-structure is similar to the cyclic cystine knot (CCK) motif, found in the cyclotides described in paper I.

    In manuscript III, the production route established in paper II was used to produce nemertides alpha 1-7. These were tested in vivo in an Artemia microwell assay as well as on an extended panel of voltage-gated sodium channels (NaV1.1 – 1.8 and BgNaV1). All seven alpha nemertides were highly active in the in vivo Artemia assay with EC50 values in the sub to low µM range. The alpha nemertides were also active in the NaVs tested. However, differences in the activity profiles were observed, indicating an opportunity for future optimization of alpha nemertides to reach higher specificity to certain NaV subtypes.

    In manuscript IV, the exploration of nemertide toxins was extended to include the Antarctic P. corrugatus. Resulting findings include a set of cysteine-rich peptides, some similar to the nemertides previously discovered in paper II. Two purified peptides and one fraction were evaluated for their membranolytic activity.

    Delarbeten
    1. Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae)
    Öppna denna publikation i ny flik eller fönster >>Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae)
    2015 (Engelska)Ingår i: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 117, s. 527-536Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Plants from Violaceae produce cyclotides, peptides characterized by a circular peptide backbone and a cystine knot. This signature motif gives stability that can harness a wide spectrum of biological activities, with implications in plant defense and with applications in medicine and biotechnology. In the current work, cyclotide expressing in vitro cultures were established from Viola uliginosa. These cultures are useful models for studying biosynthesis of cyclotides and can also be used in their production. The cyclotide expression pattern is shown to be dependent on exogenous plant growth regulators, both on peptide and gene expression levels. The highest yields of cyclotides were obtained on media containing only a cytokinin and were correlated with storage material accumulation. Exposure to auxins decreased cyclotide production and caused shifting of the biosynthesis pattern to root specific cyclotides. The response to stimuli in terms of cyclotide expression pattern appears to be developmental, and related to polar auxin transportation and the auxin/cytokinin ratio regulating tissue differentiation. By the use of whole transcriptome shotgun sequencing (WTSS) and peptidomics, 20 cyclotide sequences from V. uliginosa (including 12 new) and 12 complete precursor proteins could be identified. The most abundant cyclotides were cycloviolacin O3 (CyO3), CyO8 and CyO13. A suspension culture was obtained that grew exponentially with a doubling time of approximately 3 days. After ten days of growth, the culture provided a yield of more than 4 mg CyO13 per gram dry mass.

    Nyckelord
    Viola uliginosa (Violaceae), Cyclotides, In vitro culture, Plant growth regulators, Whole transcriptome shotgun sequencing, Mass spectrometry
    Nationell ämneskategori
    Botanik Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-264668 (URN)10.1016/j.phytochem.2015.07.016 (DOI)000361253300055 ()26246035 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 621-2007-5167Stiftelsen för strategisk forskning (SSF), F06-0058
    Tillgänglig från: 2015-10-16 Skapad: 2015-10-15 Senast uppdaterad: 2019-08-15
    2. Peptide ion channel toxins from the bootlace worm, the longest animal on Earth
    Öppna denna publikation i ny flik eller fönster >>Peptide ion channel toxins from the bootlace worm, the longest animal on Earth
    Visa övriga...
    2018 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 4596Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Polypeptides from animal venoms have found important uses as drugs, pharmacological tools, and within biotechnological and agricultural applications. We here report a novel family of cystine knot peptides from nemertean worms, with potent activity on voltage-gated sodium channels. These toxins, named the alpha-nemertides, were discovered in the epidermal mucus of Lineus longissimus, the 'bootlace worm' known as the longest animal on earth. The most abundant peptide, the 31-residue long alpha-1, was isolated, synthesized, and its 3D NMR structure determined. Transcriptome analysis including 17 species revealed eight alpha-nemertides, mainly distributed in the genus Lineus. alpha-1 caused paralysis and death in green crabs (Carcinus maenas) at 1 mu g/kg (similar to 300 pmol/kg). It showed profound effect on invertebrate voltage-gated sodium channels (e.g. Blattella germanica Na(v)1) at low nanomolar concentrations. Strong selectivity for insect over human sodium channels indicates that a-nemertides can be promising candidates for development of bioinsecticidal agents.

    Ort, förlag, år, upplaga, sidor
    NATURE PUBLISHING GROUP, 2018
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-351585 (URN)10.1038/s41598-018-22305-w (DOI)000428029600001 ()29567943 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2014-3327]
    Tillgänglig från: 2018-05-29 Skapad: 2018-05-29 Senast uppdaterad: 2019-08-15Bibliografiskt granskad
    3. Functional characterization of the nemertide alpha family of peptide toxins
    Öppna denna publikation i ny flik eller fönster >>Functional characterization of the nemertide alpha family of peptide toxins
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Farmakologi och toxikologi
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-390850 (URN)
    Forskningsfinansiär
    Vetenskapsrådet, 2014-3327Vetenskapsrådet, 2018-005403Forskningsrådet Formas, 2018-00613
    Tillgänglig från: 2019-08-15 Skapad: 2019-08-15 Senast uppdaterad: 2019-08-15
    4. Peptide toxins from the Antarctica: the nemertean predator and scavenger Parborlasia corrugatus
    Öppna denna publikation i ny flik eller fönster >>Peptide toxins from the Antarctica: the nemertean predator and scavenger Parborlasia corrugatus
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Farmakologi och toxikologi
    Forskningsämne
    Farmakognosi; Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-390880 (URN)
    Forskningsfinansiär
    Vetenskapsrådet, 2014-3327Vetenskapsrådet, 2018-005403Forskningsrådet Formas, 2018-00613
    Tillgänglig från: 2019-08-15 Skapad: 2019-08-15 Senast uppdaterad: 2019-08-15
  • 152.
    Jacobsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Peigneur, Steve
    University of Leuven (KU Leuven), Toxicology and Pharmacology.
    Håkan, Andersson
    Karolinska Institutet, Department of Medical Biochemistry and Biophysics, 2Division of Molecular Structural Biology.
    Laborde, Quentin
    Linnaeus University, Department of Chemistry and Biomedical Sciences.
    Strand, Malin
    Swedish University of Agricultural Sciences, Swedish Species Information Centre.
    Tytgat, jan
    University of Leuven (KU Leuven), Toxicology and Pharmacology.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Functional characterization of the nemertide alpha family of peptide toxinsManuskript (preprint) (Övrigt vetenskapligt)
  • 153.
    Jacobsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Andersson, Håkan S.
    Karolinska Institutet, Department of Medical Biochemistry and Biophysics, 2Division of Molecular Structural Biology.
    Avila, Conxita
    University of Barcelona, Faculty of Biology, Department of Evolutionary Biology, Ecology, and Environmental Sciences, and Biodiversity Research Institute (IrBIO).
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Peptide toxins from the Antarctica: the nemertean predator and scavenger Parborlasia corrugatusManuskript (preprint) (Övrigt vetenskapligt)
  • 154. Jensen, Lars Juhl
    et al.
    Skovgaard, Marie
    Sicheritz-Pontén, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Jørgensen, Merete Kjær
    Lundegaard, Chrstiane
    Pedersen, Corinna Cavan
    Petersen, Nanna
    Ussery, David
    Analysis of two large functionally uncharacterized regions in theMethanopyrus kandleri AV19 genome2003Ingår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 4, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: For most sequenced prokaryotic genomes, about a third of the protein coding genes annotated are "orphan proteins", that is, they lack homology to known proteins. These hypothetical genes are typically short and randomly scattered throughout the genome. This trend is seen for most of the bacterial and archaeal genomes published to date. RESULTS: In contrast we have found that a large fraction of the genes coding for such orphan proteins in the Methanopyrus kandleri AV19 genome occur within two large regions. These genes have no known homologs except from other M. kandleri genes. However, analysis of their lengths, codon usage, and Ribosomal Binding Site (RBS) sequences shows that they are most likely true protein coding genes and not random open reading frames.CONCLUSIONS: Although these regions can be considered as candidates for massive lateral gene transfer, our bioinformatics analysis suggests that this is not the case. We predict many of the organism specific proteins to be transmembrane and belong to protein families that are non-randomly distributed between the regions. Consistent with this, we suggest that the two regions are most likely unrelated, and that they may be integrated plasmids.

  • 155.
    Johansson, S.
    et al.
    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.
    Lindholm, P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Ek, B.
    Thunberg, E.
    Samuelsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    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.
    Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells2003Ingår i: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 60, nr 1, s. 165-175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Four novel proteins (phoratoxins C-F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.

  • 156.
    Johansson, Senia
    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.
    Luijendijk, Teus
    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.
    Claeson, Per
    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.
    A neutrophil multitarget functional bioassay to detect anti-inflammatory natural products2002Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 65, nr 1, s. 32-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A multitarget functional bioassay was optimized as a method for detecting substances interacting with the inflammatory process of activated neutrophil granulocytes, mainly to release elastase detected by p-nitroanilide (pNA) formation. Using this bioassay, 100 fractionated extracts of 96 plants were screened, with results presented in a manner that links recorded biological activity to phylogenetic information. The plants were selected to represent a major part of the angiosperms, with emphasis on medicinal plants, Swedish anti-inflammatory plants, and plants known to contain peptides. Of the tested extracts, 41% inhibited pNA formation more than 60%, and 3% stimulated formation. The extract of Digitalbis purpurea enhanced pNA formation, and digitoxin, the active compound, was isolated and identified. Plant extracts that exhibited potent nonselective inhibition (> 80% inhibition) were evaluated further for direct inhibition of isolated elastase and trypsin enzyme. The inhibitory effect of most tested extracts on the isolated enzyme elastase was similar to that of PAF- and fMLP-induced pNA formation. Compared to trypsin, inhibition of elastase by extracts of Rubus idaeus and Tabernaemontana dichotoma was significantly higher (80% and 99%, respectively). Inhibition of trypsin by the extract of Reseda luteola was high 97%. Orders such as Lamiales and Brassicales were shown to include a comparably high proportion of plants with inhibitory extracts.

  • 157. Johansson, Senia
    et al.
    Lindholm, Petra
    Uppsala universitet, Medicinska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gullbo, Joachim
    Larsson, Rolf
    Bohlin, Lars
    Claeson, Per
    Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells2001Ingår i: Anticancer Drugs, Vol. 12, nr 5, s. 475-483Artikel i tidskrift (Refereegranskat)
  • 158.
    Johansson, Senia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lindholm, Petra
    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.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    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.
    Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells2001Ingår i: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 12, nr 5, s. 475-83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.

  • 159. Johnson, Ann-Louise
    et al.
    Bergman, Jan
    Sjögren, Martin
    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.
    Synthesis of barettin2004Ingår i: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 60, nr 4, s. 961-965Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The indole alkaloid barettin (with bromine in 6-position), isolated from the marine sponge Geodia Barretti, has been synthesised via a Horner-Wadsworth-Emmons type reaction from 6-bromoindole-3-carboxaldehyde to introduce the dehydro-functionality. Subsequent deprotection and cyclisation afforded the natural product in Z-conformation.

  • 160.
    Karimian, Hamed
    et al.
    Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia..
    Fadaeinasab, Mehran
    Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia..
    Moghadamtousi, Soheil Zorofchian
    Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia..
    Hajrezaei, Maryam
    Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia..
    Zahedifard, Maryam
    Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia..
    Razavi, Mahboubeh
    Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia..
    Safi, Sher Zaman
    Univ Malaya, Fac Med, Dept Med, Kuala Lumpur 50603, Malaysia..
    Mohan, Syam
    Jazan Univ, Med Res Ctr, Jazan, Saudi Arabia..
    Khalifa, Shaden A. M.
    Karolinska Univ Hosp, Dept Expt Hematol, Stockholm, Sweden..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Karolinska Univ Hosp, Dept Expt Hematol, Stockholm, Sweden.
    Abdulla, Mahmood Amin
    Univ Malaya, Fac Med, Dept Biomed Sci, Kuala Lumpur 50603, Malaysia..
    Ali, Hapipah Mohd
    Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia..
    Noordin, Mohamad Ibrahim
    Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia..
    The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach2015Ingår i: Cellular Physiology and Biochemistry, ISSN 1015-8987, E-ISSN 1421-9778, Vol. 36, nr 3, s. 988-1003Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8 beta-hydroxyl-4 beta, 15-dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis. 

  • 161. Karlsson, Pernilla C
    et al.
    Huss, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Jenner, Andrew
    Halliwell, Barry
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Rafter, Joseph J
    Human fecal water inhibits COX-2 in colonic HT-29 cells: role of phenolic compounds2005Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 135, nr 10, s. 2343-2349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The inducible enzyme cyclooxygenase-2 (COX-2) plays a major role in the regulation of inflammation and possibly in the development of colon cancer. The aim of the present study was to screen for COX-2 inhibitors in samples of fecal water (the aqueous phase of feces) and investigate whether phenolic compounds are responsible for any observed effects on COX-2. Volunteers (n = 20) were recruited and asked to supply a 24-h stool sample. Fecal water samples were prepared and analyzed by GC-MS for their content of phenolic compounds. These samples were also evaluated for their effects on COX-2 protein levels (Western blot) and prostaglandin (PG)E2 production in tumor necrosis-alpha-stimulated HT-29 cells and pure enzymatic activity in a COX-2-catalyzed prostaglandin biosynthesis in vitro assay. The major phenolic compounds identified were phenylpropionic acid, phenylacetic acid, cinnamic acid, and benzoic acid derivatives. Of 13 fecal water samples analyzed, 12 significantly decreased PGE2 production (range 5.4-39.7% inhibition, P-value < 0.05) compared with control cells and 13 of 14 samples analyzed decreased COX-2 protein levels in HT-29 cells (19-63% inhibition). Of the 20 fecal water samples, 2 also weakly inhibited enzymatic activity of purified COX-2 (22-24% inhibition). Three compounds identified in fecal water, 3-phenylpropionic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, decreased the protein level at 250 micromol/L (15-62% inhibition). This study shows for the first time that human fecal water contains components that can affect both the COX-2 protein level and enzymatic activity.

  • 162.
    Kelly, Michelle
    et al.
    Natl Inst Water & Atmospher Res Ltd, Coasts & Oceans Natl Ctr, Private Bag 99940, Auckland, New Zealand..
    Cardenas, Paco
    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.
    An unprecedented new genus and family of Tetractinellida (Porifera, Demospongiae) from New Zealand's Colville Ridge, with a new type of mitochondrial group I intron2016Ingår i: Zoological Journal of the Linnean Society, ISSN 0024-4082, E-ISSN 1096-3642, Vol. 177, nr 2, s. 335-352Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A remarkable sponge with unprecedented megascleres and systematic affinities was collected recently from a previously unidentified volcano on Colville Ridge to the north-east of New Zealand. The sponge has the appearance of a tetillid sponge (family Tetillidae Sollas, 1886) with a perfectly spherical external form, radiating internal skeleton of huge oxeas and triaenes, and microspined sigmaspires as microscleres. The triaene megascleres, however, are unprecedented in their form and ornamentation; they are huge clubbed orthotriaenes the upper third of which is acanthose. Stupenda singularis gen. et sp. nov. is described here and the phylogenetic affinity and taxonomic position of this unique sponge is explored in relation to a broad range of tetractinellid sponges (order Tetractinellida Marshall, 1876) using the Folmer + Erpenbeck fragment of the cytochrome c oxidase subunit I (COI) gene and a nearly complete sequence of the 18S rDNA gene. Mitochondrial introns are rare in sponges but S. singularis gen. et sp. nov. possesses a mitochondrial group I intron at position 387 in COI; it hosts a putative LAGLIDADG endonuclease gene. This intron is the first of its kind in sponges: the self-splicing intron is homologous to a placozoan COI intron whereas the LAGLIDADG endonuclease gene may be related to Fungi LAGLIDADG endonuclease genes.

  • 163. Khalifa, Shaden A. M.
    et al.
    de Medina, Philippe
    Erlandsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Silvente-Poirot, Sandrine
    Poirot, Marc
    The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells2014Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 446, nr 3, s. 681-686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain. (C) 2014 Elsevier Inc. All rights reserved.

  • 164.
    Khan, T. M.
    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.
    Roy, D.
    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.
    Structure and Activity Relationship of the Echinochloa Crus-Galli Antimicrobial Peptide 12014Ingår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 20, s. S278-S279Artikel i tidskrift (Övrigt vetenskapligt)
  • 165.
    Kirkpatrick, Christine L.
    et al.
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    Broberg, Christopher A.
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    McCool, Elijah N.
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    Lee, Woo Jean
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    Chao, Alex
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    McConnell, Evan W.
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    Pritchard, David A.
    Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC USA..
    Hebert, Michael
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    Fleeman, Renee
    Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA..
    Adams, Jessie
    Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA..
    Jamil, Amer
    Univ Agr Faisalabad, Dept Biochem, Faisalabad, Pakistan..
    Madera, Laurence
    Dalhousie Univ, Dept Pathol, Halifax, NS, Canada..
    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.
    Liu, Yufeng
    Univ North Carolina Chapel Hill, Dept Biostat, Dept Genet, Dept Stat & Operat Res, Chapel Hill, NC USA.;Univ North Carolina Chapel Hill, Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Hoskin, David W.
    Dalhousie Univ, Dept Pathol, Halifax, NS, Canada..
    Shaw, Lindsey N.
    Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA..
    Hicks, Leslie M.
    Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC USA..
    The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery2017Ingår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, nr 2, s. 1194-1201Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.

  • 166. Knudsen, Steen
    et al.
    Workman, Christopher
    Sicheritz-Ponten, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Friis, Carsten
    GenePublisher: automated analysis of DNA microarray data2003Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 31, nr 13, s. 3471-3476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    GenePublisher, a system for automatic analysis of data from DNA microarray experiments, has been implemented with a web interface at http://www.cbs.dtu.dk/services/GenePublisher. Raw data are uploaded to the server together with a specification of the data. The server performs normalization, statistical analysis and visualization of the data. The results are run against databases of signal transduction pathways, metabolic pathways and promoter sequences in order to extract more information. The results of the entire analysis are summarized in report form and returned to the user.

  • 167. Koehbach, Johannes
    et al.
    O'Brien, Margaret
    Muttenthaler, Markus
    Miazzo, Marion
    Akcan, Muharrem
    Elliott, Alysha G.
    Daly, Norelle L.
    Harvey, Peta J.
    Arrowsmith, Sarah
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Smith, Terry J.
    Wray, Susan
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Dawson, Philip E.
    Craik, David J.
    Freissmuth, Michael
    Gruber, Christian W.
    Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design2013Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, nr 52, s. 21183-21188Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.

  • 168.
    Koptina, Anna
    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.
    Muhammad, Taj
    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.
    Alsmark, Cecilia
    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.
    Microwave-assisted solid phase peptide synthesis of Asteropine A2014Ingår i: Phytopharm 2014, Saint-Petersburg, Russia 3-5 July 2014 / [ed] Shabanov P.D., Saint-Petersburg, Russia, 2014, Vol. 12, s. 36-Konferensbidrag (Refereegranskat)
  • 169.
    Koptina, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Volga State Univ Technol, Yoshkar Ola 424000, Russia..
    Strese, Åke
    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.
    Alsmark, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Natl Vet Inst SVA, Dept Virol Immunobiol & Parasitol, S-75651 Uppsala, Sweden..
    Challenges to get axenic cultures of Trichomonas spp.: A new approach in eradication of contaminants and maintenance of laboratory microbiological cultures2015Ingår i: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 118, s. 25-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Contamination of microbiological and cell cultures is a major problem in many scientific and clinical laboratories as well as bioproduct manufacturers worldwide. In the current study we established a rapid (9 day) method to detect and eliminate fungal and bacterial contamination in cultures of the unicellular eukaryote Trichomonas spp. The developed method combines identification of the contaminating microorganisms using PCR and sequencing of the 16/18S regions followed by phylogenetic analysis. The next step was a phylogeny-guided selection of antibiotic treatments. We then used a two-step propidium iodide-resorufin assay to test the effect of selected antibiotics. The result was a quick and worthwhile purification of trichomonad laboratory cultures. Our workflow may also be implemented to obtain new isolates of trichomonads from clinical samples if initial broad-spectrum antibiotic therapy fails.

  • 170.
    Korinek, Michal
    et al.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Dept Biotechnol, Coll Life Sci, Kaohsiung, Taiwan..
    Tsai, Yi-Hong
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    El-Shazly, Mohamed
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Ain Shams Univ, Dept Pharmacognosy, Fac Pharm, Cairo, Egypt..
    Lai, Kuei-Hung
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Wu, Shou-Fang
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Dev Ctr Biotechnol, Nat Resource Dev Inst Pharmaceut, New Taipei, Taiwan..
    Lai, Wan-Chun
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Wu, Tung-Ying
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Chen, Shu-Li
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Wu, Yang-Chang
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Res Ctr Nat Prod & Drug Dev, Kaohsiung, Taiwan.;Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan..
    Cheng, Yuan-Bin
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Res Ctr Nat Prod & Drug Dev, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Ctr Infect Dis & Canc Res, Kaohsiung, Taiwan..
    Hwang, Tsong-Long
    Chang Gung Univ, Grad Inst Nat Prod, Coll Med, Taoyuan, Taiwan.;Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Res Ctr Food & Cosmet Safety, Coll Human Ecol, Taoyuan, Taiwan.;Chang Gung Univ Sci & Technol, Coll Human Ecol, Grad Inst Hlth Ind Technol, Taoyuan, Taiwan.;Chang Gung Mem Hosp, Dept Anesthesiol, Taoyuan, Taiwan..
    Chen, Bing-Hung
    Kaohsiung Med Univ, Dept Biotechnol, Coll Life Sci, Kaohsiung, Taiwan.;Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan.;Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan..
    Chang, Fang-Rong
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Ctr Infect Dis & Canc Res, Kaohsiung, Taiwan.;Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Res Ctr Environm Med, Kaohsiung, Taiwan.;Kaohsiung Med Univ Hosp, Canc Ctr, Kaohsiung, Taiwan..
    Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP2017Ingår i: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 8, artikel-id 356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z, 13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E, 12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R *-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14-3.73 mu M) and elastase release (IC50 1.26-4.57 mu M) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187-and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E, 12Z-octadecadienoic acid, IC50 92.4 and 49.7 mu M, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

  • 171. Kraus, Christina M
    et al.
    Neszmelyi, András
    Holly, Sándor
    Wiedemann, Beate
    Nenninger, Anneli
    Torsell, Kurt B G
    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.
    Wagner, Hildebert
    New acetylenes isolated from the bark of Heisteria acuminata1998Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 61, nr 4, s. 422-427Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Five new linear acetylenic compounds, namely, pentadeca-6,8,10-triynoic acid (1), octadeca-8,10,12-triynoic acid (2), trans-pentadec-10-en-6,8-diynoic acid (3), cis-hexadec-11-en-7,9-diynoic acid (4), and cis-octadec-12-en-7,9-diynoic acid (5), were isolated from the bark of Heisteria acuminata by bioassay-guided fractionation, using cyclooxygenase (COX) and 5-lipoxygenase (5-LO) assays as models for antiinflammatory activity. The structures of compounds 1-5 were established by NMR, MS, IR, and Raman spectroscopy. These isolated compounds were found to be potent inhibitors of COX. Compounds 4 and 5 were the most potent inhibitors of 5-LO, whereas the other compounds only showed a weak inhibition at the same concentration.

  • 172.
    Kudryashova, Elena
    et al.
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Koneru, Pratibha C.
    Ohio State Univ, Ctr Retroviral Res, Columbus, OH 43210 USA.;Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA..
    Kvaratskhelia, Mamuka
    Ohio State Univ, Ctr Retroviral Res, Columbus, OH 43210 USA.;Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA..
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lu, Wuyuan
    Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA..
    Kudryashov, Dmitri S.
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.;Ohio State Univ, Publ Hlth Preparedness Infect Dis Program, Columbus, OH 43210 USA..
    Thermodynamic instability of viral proteins is a pathogen-associated molecular pattern targeted by human defensins2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 32499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human defensins are innate immune defense peptides with a remarkably broad repertoire of anti-pathogen activities. In addition to modulating immune response, inflammation, and angiogenesis, disintegrating bacterial membranes, and inactivating bacterial toxins, defensins are known to intercept various viruses at different stages of their life cycles, while remaining relatively benign towards human cells and proteins. Recently we have found that human defensins inactivate proteinaceous bacterial toxins by taking advantage of their low thermodynamic stability and acting as natural "anti-chaperones", i.e. destabilizing the native conformation of the toxins. In the present study we tested various proteins produced by several viruses (HIV-1, PFV, and TEV) and found them to be susceptible to destabilizing effects of human alpha-defensins HNP-1 and HD-5 and the synthetic theta-defensin RC-101, but not beta-defensins hBD-1 and hBD-2 or structurally related plant-derived peptides. Defensin-induced unfolding promoted exposure of hydrophobic groups otherwise confined to the core of the viral proteins. This resulted in precipitation, an enhanced susceptibility to proteolytic cleavage, and a loss of viral protein activities. We propose, that defensins recognize and target a common and essential physico-chemical property shared by many bacterial toxins and viral proteins - the intrinsically low thermodynamic protein stability.

  • 173.
    Kummala, T
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Vuorela, H
    Johansson, S
    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.
    Vasange, M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Inhibitory activity of a series of coumarins on neutrophil elastase secretion induced by platelet activating factor (PAF) and the chemotactic peptide fMLP.1998Ingår i: Pharmaceutical and pharmacological letters, Vol. 8, s. 144-Artikel i tidskrift (Refereegranskat)
  • 174.
    Lai, Kuei-Hung
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Studies on anti-leukemic terpenoids from medicinal mushrooms and marine sponges with ChemGPS-NP-based targets investigation of lead compounds2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis investigates the anti-leukemic activity of terpenoids isolated from medicinal mushrooms and marine sponges, as well as their possible targets and mechanisms of action.

    In the first section, we focused on studying the triterpenoidal components of three triterpenoid-enriched medicinal mushrooms Antrodia cinnamomea, Ganoderma lucidum, and Poria cocos, which have been used in folk medicine for centuries and also developed into several contemporary marketed products. We isolated the major and characteristic triterpenoids from these mushrooms, together with six new lanostanoids (II-1II-6). The anti-leukemic activity of the isolates was evaluated in vitro using MTT proliferative assay and seven of them exhibited potential anti-leukemic effect. The active lead compounds were further subjected to computational analyses utilizing the ChemGPS-NP tool. We established a database for the anti-leukemic relevant chemical space of triterpenoids isolated from these three medicinal mushrooms, which could be used as a reference database for further research on anti-leukemic triterpenoids. Our results indicated that the anti-leukemic effect of the active lead compounds was mediated not only through topoisomerases inhibition but also through inhibiting DNA polymerases.

    The second and third sections focused on isolation of anti-leukemic sesterterpenoids from sponges. The investigation of Carteriospongia sp. led to the isolation of two new scalarane-type sesterterpenoids (III-1 and III-2) and one known tetraprenyltoluquinol-related metabolite (III-3). All isolates exhibit an apoptotic mechanism of action against Molt 4 cells, found to be mediated through the disruption of the mitochondrial membrane potential (MMP) and inhibition of topoisomerase IIα expression. Detailed investigation of the apoptotic mechanism of action using molecular docking analysis revealed that compound III-1 might target Hsp90 protein. The apoptotic-inducing effect of III-3 was supported by in vivo experiment by suppressing the volume of xenograft tumor growth (47.58%) compared with the control.

    In the final section of this thesis we studied manoalide and its derivatives, sesterterpenoids isolated from the sponge Luffariella sp.. Manoalide has been studied as a potential anti-inflammatory agent for the last thirty years with more than 200 publications and 40 patents. However, the configurations at positions 24 and 25 were never revealed. In the current study, ten manoalide-type sesterterpenoids (IV-1IV-10) were isolated from Luffariella sp. and their stereoisomers at positions 24 and 25 were identified and separated for the first time. The configuration at positions 24 and 25 showed to have a significant effect on the anti-leukemic activity of manoalide derivatives, with the 24R,25S-isomer exhibiting the most potent anti-leukemic activity. The apoptotic mechanism of action of compound IV-7 against Molt 4 cells was investigated, and the compound was found to trigger MMP disruption and intracellular reactive oxygen species (ROS) generation. Compound IV-7 also inhibited activity against both human topoisomerases, I and II. The in vivo experiment further supported the anti-leukemic effect of IV-7 with a 66.11% tumor volume suppression compared to the control.

    Delarbeten
    1. Cytotoxic Lanostanoids from Poria cocos
    Öppna denna publikation i ny flik eller fönster >>Cytotoxic Lanostanoids from Poria cocos
    Visa övriga...
    2016 (Engelska)Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 79, nr 11, s. 2805-2813Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (2), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (3), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (4), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (5), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (6), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher's method. The antiproliferative activity of the isolated compounds (except 3 and 4) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid (9), dehydroeburicoic acid (12), pachymic acid (14), and lanosta-7,9(11),24-trien-21-oic acid (20) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed antiproliferative effects against Molt 4 (IC50 13.8 and 14.3 μM) and HL 60 (IC50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the antiproliferative activity.

    Nationell ämneskategori
    Biokemi och molekylärbiologi Läkemedelskemi Farmaceutiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-317526 (URN)10.1021/acs.jnatprod.6b00575 (DOI)000394410600006 ()27808511 (PubMedID)
    Anmärkning

    De 2 första författarna delar förstaförfattarskapet.

    Tillgänglig från: 2017-03-15 Skapad: 2017-03-15 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    2. Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90
    Öppna denna publikation i ny flik eller fönster >>Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90
    Visa övriga...
    2016 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 36170Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Two new scalarane sesterterpenoids, 12 beta-(3'beta-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12 beta-(3'beta-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 mu g/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase II alpha expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70(S6k), NF kappa B, Raf-1, p-GSK3 beta, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.

    Nationell ämneskategori
    Cell- och molekylärbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
    Identifikatorer
    urn:nbn:se:uu:diva-308635 (URN)10.1038/srep36170 (DOI)000386462100001 ()27796344 (PubMedID)
    Tillgänglig från: 2016-11-30 Skapad: 2016-11-29 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    3. ChemGPS-NP study on antileukemic triterpenoids from widely-used medicinal mushrooms in Asia
    Öppna denna publikation i ny flik eller fönster >>ChemGPS-NP study on antileukemic triterpenoids from widely-used medicinal mushrooms in Asia
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Läkemedelskemi Farmaceutiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-317552 (URN)
    Tillgänglig från: 2017-03-16 Skapad: 2017-03-16 Senast uppdaterad: 2018-01-13
    4. Separation and identification on stereoisomers of manoalide derivatives and their configuration-depending antileukemic effects in vitro and in vivo
    Öppna denna publikation i ny flik eller fönster >>Separation and identification on stereoisomers of manoalide derivatives and their configuration-depending antileukemic effects in vitro and in vivo
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Farmakologi och toxikologi Cell- och molekylärbiologi Farmaceutiska vetenskaper Läkemedelskemi
    Identifikatorer
    urn:nbn:se:uu:diva-317553 (URN)
    Tillgänglig från: 2017-03-16 Skapad: 2017-03-16 Senast uppdaterad: 2018-01-13
  • 175.
    Lai, Kuei-Hung
    et al.
    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.
    ChemGPS-NP study on antileukemic triterpenoids from widely-used medicinal mushrooms in AsiaManuskript (preprint) (Övrigt vetenskapligt)
  • 176.
    Lai, Kuei-Hung
    et al.
    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.
    Separation and identification on stereoisomers of manoalide derivatives and their configuration-depending antileukemic effects in vitro and in vivoManuskript (preprint) (Övrigt vetenskapligt)
  • 177.
    Lai, Kuei-Hung
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan..
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lu, M. C.
    Natl Dong Hwa Univ, Grad Inst Marine Biotechnol, Pingtung, Taiwan.;Natl Museum Marine Biol & Aquarium, Pingtung, Taiwan..
    Du, Y. C.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan..
    El-Shazly, M.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan.;Ain Shams Univ, Fac Pharm, Dept Pharmacognosy & Nat Prod Chem, Cairo, Egypt..
    Wu, T. Y.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan..
    Hsu, Y. M.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan..
    Henz, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Chang, F. R.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan.;Kaohsiung Med Univ Hosp, Canc Ctr, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Res Ctr Nat Prod & New Drug, Kaohsiung, Taiwan.;Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung 80424, Taiwan..
    Wu, Y. C.
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung, Taiwan.;China Med Univ, Coll Pharm, Sch Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan.;China Med Univ Hosp, Ctr Mol Med, Taichung, Taiwan..
    Antileukemic lanostanoids from Poria cocos2015Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 81, nr 16, s. 1418-1418Artikel i tidskrift (Övrigt vetenskapligt)
  • 178.
    Lai, Kuei-Hung
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lu, M. C.
    Natl Dong Hwa Univ, Grad Inst Marine Biotechnol, Pingtung, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung, Taiwan..
    Du, Y. C.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    El-Shazly, M.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Ain Shams Univ, Fac Pharm, Dept Pharmacognosy & Nat Prod Chem, Cairo, Egypt..
    Wu, T. Y.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Hsu, Y. M.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan..
    Henz, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Chang, F. R.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung, Taiwan.;Kaohsiung Med Univ, Res Ctr Nat Prod & New Drug, Kaohsiung, Taiwan.;Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung 80424, Taiwan..
    Wu, Y. C.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan.;China Med Univ, Sch Pharm, Coll Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan.;China Med Univ Hosp, Ctr Mol Med, Taichung, Taiwan..
    Antileukemic lanostanoids from Poria cocos2015Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 81, nr 16, s. 1453-1453Artikel i tidskrift (Övrigt vetenskapligt)
  • 179.
    Lai, Kuei-Hung
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan.;Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Liu, Yi-Chang
    Kaohsiung Med Univ Hosp, Dept Internal Med, Div Hematol Oncol, Kaohsiung 807, Taiwan.;Kaohsiung Med Univ, Coll Med, Fac Med, Dept Internal Med, Kaohsiung 807, Taiwan..
    Su, Jui-Hsin
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    El-Shazly, Mohamed
    Ain Shams Univ, Dept Pharmacognosy & Nat Prod Chem, Fac Pharm, Org African Unity St, Cairo 11566, Egypt..
    Wu, Chih-Fung
    Kaohsiung Med Univ Hosp, Dept Surg, Div Surg Oncol, Kaohsiung 807, Taiwan..
    Du, Ying-Chi
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan.;Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Hsu, Yu-Ming
    Kaohsiung Med Univ, Coll Pharm, Grad Inst Nat Prod, Kaohsiung 807, Taiwan..
    Yang, Juan-Cheng
    China Med Univ, Sch Pharm, Coll Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan..
    Weng, Ming-Kai
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan..
    Chou, Chia-Hua
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    Chen, Guan-Yu
    China Med Univ, Sch Pharm, Coll Pharm, Taichung, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan..
    Chen, Yu-Cheng
    China Med Univ, PhD Program Canc Biol & Drug Discovery, Taichung, Taiwan.;Acad Sinica, Taichung, Taiwan..
    Lu, Mei-Chin
    Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 944, Taiwan.;Natl Museum Marine Biol Aquarium, Pingtung 944, Taiwan..
    Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp902016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 36170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two new scalarane sesterterpenoids, 12 beta-(3'beta-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12 beta-(3'beta-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 mu g/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase II alpha expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70(S6k), NF kappa B, Raf-1, p-GSK3 beta, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.

  • 180.
    Lai, Kuei-Hung
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Lu, Mei-Chin
    Du, Ying-Chi
    El-Shazly, Mohamed
    Wu, Tung-Ying
    Hsu, Yu-Ming
    Henz, Astrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Yang, Juan-Cheng
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Chang, Fang-Rong
    Wu, Yang-Chang
    Cytotoxic Lanostanoids from Poria cocos2016Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 79, nr 11, s. 2805-2813Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (2), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (3), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (4), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (5), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (6), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher's method. The antiproliferative activity of the isolated compounds (except 3 and 4) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid (9), dehydroeburicoic acid (12), pachymic acid (14), and lanosta-7,9(11),24-trien-21-oic acid (20) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed antiproliferative effects against Molt 4 (IC50 13.8 and 14.3 μM) and HL 60 (IC50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the antiproliferative activity.

  • 181.
    Larik, Fayaz Ali
    et al.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Shahzad, Danish
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Faisal, Muhammad
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Mehfooz, Haroon
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Channar, Pervaiz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives2017Ingår i: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 118, s. 76-92Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.

  • 182.
    Larsson, Josefin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Gottfries, Johan
    Bohlin, Lars
    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.
    Expanding the ChemGPS chemical space with natural products2005Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 68, nr 7, s. 985-991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.

  • 183.
    Larsson, Josefin
    et al.