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  • 51.
    Henz Ryen, Astrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Kogej, Thierry
    Structural classification and scaffold diversity of sesquiterpene lactones in the angiospermsIngår i: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Sesquiterpene lactones (STLs) present one of the largest groups of plant specialized metabolites with a wide range of biological activities. They are a valuable source for new plant derived drugs and drug leads since they contain several important chemical properties responsible for their versatile therapeutic potential.

    The aim of this study was to analyze and compare the chemical diversity of all types of STLs in different plant groups, both qualitatively and quantitatively. For this purpose, over 5,200 STLs have been compiled and their plant origin has been recorded, resulting in a comprehensive dataset comprising over 8,600 entries. An overview of skeleton classes and their distribution among plant families was given by assigning the STLs to their major classes. An extensive scaffold diversity analysis was performed based on the molecular framework of these compounds using established metrics. Furthermore, molecular diversity and similarity was assessed via 2D fingerprint and clustering analysis.

    The results highlighted significant differences in the degree of chemical diversity. It was demonstrated that the investigated plant families have tendencies to produce certain types of skeletons. The quantity and distribution of skeleton classes was determined per plant family and genus, as well as the proportions of skeleton classes to other STL producing families. Analyzing the scaffold diversity showed that they possessed specific sets of molecular frameworks with a considerable variation in their frequency of occurrence. Even if many plant families produce STLs belonging to the same skeleton class, their corresponding molecular frameworks differ. Clustering analysis confirmed the known large structural diversity and revealed similarities and differences of the compounds. The metrics employed enabled to qualitatively divide STLs into smaller groups with similar structural features, which reflected biologically and chemically different STLs and pointed out the differentiation of various plant groups, down to the taxonomic rank of the species.

    Taken together, these analyses provided a comprehensive insight into scaffold and molecular diversity of STLs. Due to the detailed taxonomic annotation, the distinct distribution of different types of STLs was captured. This dataset represents the latest detailed compilation of STLs in the angiosperms, which can be used as a basis for further chemoinformatic or chemosystematic analyses. To provide an example of potential implementations, the results were utilized in a phylogenetic exploration of these metabolites.

  • 52.
    Henz Ryen, Astrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Charting Angiosperm Chemistry: Evolutionary Perspective on Specialized Metabolites Reflected in Chemical Property Space2019Ingår i: Journal of Natural Products, ISSN 0163-3864, E-ISSN 1520-6025, Vol. 82, nr 4, s. 798-812Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plants possess an outstanding chemical diversity of specialized metabolites developed to adapt to environmental niches and increase fitness. The observed diversity is hypothesized to result from various evolutionary mechanisms, such as the continuous branching off and extension of existing biosynthetic pathways or enhanced levels of catalytic promiscuity in certain enzymes. In this study, ChemGPS-NP has been employed to chart the distribution and diversity of physicochemical properties for selected types of specialized metabolites from the angiosperms. Utilizing these charts, it is analyzed how different properties of various types of specialized metabolites change in different plant groups, and the chemical diversity from the volume they occupy in chemical property space is evaluated. In this context, possible underlying evolutionary mechanisms are discussed, which could explain the observed distribution and behavior in chemical property space. Based on these studies, it is demonstrated that evolutionary processes in plant specialized metabolism and the resultant metabolic diversification are reflected in chemical property space.

  • 53.
    Hussain, Afzal
    et al.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    Oves, Mohammad
    King Abdulaziz Univ, Ctr Excellence Environm Studies, Jeddah 21589, Saudi Arabia.
    Alajmi, Mohamed F.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    Hussain, Iqbal
    Jubail Ind Coll, Dept Gen Studies, Jubail Ind City 31961, Jubail, Saudi Arabia.
    Amir, Samira
    Alfaisal Univ, Dept Chem, Coll Sci & Gen Studies, Riyadh 11451, Saudi Arabia.
    Ahmed, Jahangeer
    King Saud Univ, Dept Chem, Coll Sci, Riyadh 11451, Saudi Arabia.
    Rehman, Md Tabish
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Ali, Imran
    Taibah Univ, Dept Chem, Coll Sci, Al Medina Al Munawara 41477, Saudi Arabia;Jamia Millia Islamia, Dept Chem, New Delhi, India.
    Biogenesis of ZnO nanoparticles using Pandanus odorifer leaf extract: anticancer and antimicrobial activities2019Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 9, nr 27, s. 15357-15369Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The continuously increasing incidence rates of cancer and infectious diseases are open threats to the sustainable survival of animals and humans. In the last two decades, the demands of nanomaterials as modern therapeutic agents have increased. In this study, biogenic zinc oxide nanoparticles (ZnO NPs) were developed from aqueous Pandanus odorifer leaf extract (POLE) and characterized using modern methods and tools, such as electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy and UV-vis spectroscopy, which indicated the formation of very pure, spherical NPs approximately 90 nm in size. The anticancer activity of the ZnO NPs was evaluated by MTT and neutral red uptake (NRU) assays in MCF-7, HepG2 and A-549 cells at different doses (1, 2, 5, 10, 25, 50, 100 g ml(-1)). Moreover, the morphology of the treated cancer cells was examined by phase contrast microscopy. The results suggest that the synthesized ZnO NPs inhibited the growth of the cells when applied a concentration from 50-100 g ml(-1). Moreover, the biogenic ZnO NPs were analysed as an antimicrobial agent against pathogenic bacteria. The highest antibacterial activity was observed against Gram-positive Bacillus subtilis (26 nm) and Gram-negative Escherichia coli (24 mm) at 50 g per well. Complete bacterial growth (100%) vanished 100% upon treatment with ZnO NPs at 85 g ml(-1). Overall, POLE mediated derived biogenic ZnO NPs could serve as a significant anticancer and antimicrobial agent and be used in the development of novel drugs and skin care products.

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  • 54.
    Hussein, Juma
    et al.
    Systematisk biologi, Systematic Biology.
    Chi, Celestine N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Tibell Savić, Sanja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Tibuhwa, Donatha
    University of Dar es Salaam, Department of molecular Biology and Biotechnology.
    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.
    Rosengren, Johan
    Wedén, Christina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik. 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. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Cysteine-rich peptide from the gigantic edible mushroom Kusaghiporia usambarensis (Laetiporaceae)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Cysteine-rich peptides are produced by various organisms across all kingdoms and have triggered an interest in isolation of molecules for novel drug development. In this study, we report a novel cysteine-rich peptide, kusaghitide, isolated from the gigantic medicinal mushroom Kusaghiporia usambarensis. It is highly expressed in the K. usambarensis transcriptome and it is the most abundant compound in the methanol-water extract. The 54 amino acid residue long peptide was isolated through aqueous methanol 50% and a sample was reduced, alkylated and cleaved enzymatically. De novo sequencing was done by LC-MS/MS and obtained sequences were used for mining the transcriptome to search for the complete gene. The peptide was recombinantly expressed in One Shot BL21 Star Escherichia coli using lysogenic broth and minimal media. Its 3D NMR structure was determined using 2D and 3D NMR. Three hypothetical protein sequences similar to kusaghitide originate from Laetiporus sulphureusWolfiporia cocos and Sparassis crispa with per cent similarity of 76% and 58% and 53% respectively and were found by BLAST search in the NCBI database. Kusaghitide did not inhibit the growth of either Escherichia coli or Staphylococcus aureus. This is first report of a peptide from K. usambarensis in Laetiporaceae.

  • 55.
    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
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  • 56.
    Jacobsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Andersson, H. S.
    Linnaeus Univ, Dept Chem & Biomed Sci, Ctr Biomat Chem, Kalmar, Sweden..
    Strand, M.
    Swedish Univ Agr Sci, Swedish Species Informat Ctr, Uppsala, Sweden..
    Lebbe, E.
    Univ Leuven KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Eriksson, Camilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Peigneur, S.
    Univ Leuven KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Rosengren, J.
    Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia..
    Tytgat, J.
    Univ Leuven KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Peptide toxins from the longest animal on earth2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Artikel i tidskrift (Övrigt vetenskapligt)
  • 57.
    Jacobsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Andersson, Håkan S.
    Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, Kalmar, Sweden..
    Strand, Malin
    Swedish Univ Agr Sci, Swedish Species Informat Ctr, Uppsala, Sweden..
    Peigneur, Steve
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Eriksson, Camilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Lodén, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Shariatgorji, Mohammadreza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Andrén, Per E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lebbe, Eline K. M.
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Rosengren, K. Johan
    Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia..
    Tytgat, Jan
    Univ Leuven, KU Leuven, Toxicol & Pharmacol, O&N 2,POB 992,Herestr 49, B-3000 Leuven, Belgium..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Peptide ion channel toxins from the bootlace worm, the longest animal on Earth2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 4596Artikel i tidskrift (Refereegranskat)
    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.

    Ladda ner fulltext (pdf)
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  • 58.
    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)
  • 59.
    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)
  • 60.
    Kanwal, Nayab
    et al.
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.
    Siddiqui, Amna Jabbar
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.
    Ul Haq, Faraz
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Musharraf, Syed Ghulam
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.
    Two-stage mass spectrometry approach for the analysis of triterpenoid glycosides in Fagonia indica2018Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 8, nr 71, s. 41023-41031Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Triterpenoid glycosides are molecules widely distributed in plants and have shown a wide range of biological activities against various diseases. This paper describes the qualitative and quantitative analysis of triterpenoid glycoside (saponins) using a two-stage mass spectrometry approach in five samples of Fagonia indica collected from various parts of the country. In the first stage, triterpenoid glycosides were identified using liquid chromatography high-resolution mass spectrometry using UHPLC-QTOF-MS system. In the second stage, compounds were quantified using a multiple reaction monitoring (MRM) approach using an UHPLC-QQQ-MS system. Fagonia indica has shown a wide range of biological activities and found to be rich in saponin or triterpenoid glycoside constituents. A total of thirteen triterpenoid saponins were identified based on high-resolution analysis, MS/MS and database comparison, while six of them were simultaneously quantified using the multiple reaction monitoring (MRM) approach. The results indicate that the samples share a similar UHPLC pattern, however, the amount of these saponins in samples varies greatly. Compound 4i.e. nayabin D was the major constituent (1.4-3.8 g g(-1)) among the six analyzed compounds. The results demonstrated that the developed multi-compound determination in combination with a fingerprint analysis method is rapid, accurate, precise and sensitive and can be utilized for quality control and high-throughput quantification of various saponins in Fagonia indica may be extended to other plant species.

  • 61.
    Kelly, Michelle
    et al.
    Natl Inst Water & Atmospher Res, Coasts & Oceans Natl Ctr, POB 109-695, Auckland, New Zealand.
    Cardenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Rush, Nicola
    Natl Inst Water & Atmospher Res, Coasts & Oceans Natl Ctr, POB 109-695, Auckland, New Zealand.
    Sim-Smith, Carina
    Natl Inst Water & Atmospher Res, Coasts & Oceans Natl Ctr, POB 109-695, Auckland, New Zealand.
    Macpherson, Diana
    Natl Inst Water & Atmospher Res, Coasts & Oceans Natl Ctr, Private Bag 14901, Wellington, New Zealand.
    Page, Mike
    Natl Inst Water & Atmospher Res, Coasts & Oceans Natl Ctr, POB 893, Nelson, New Zealand.
    Bell, Lori J.
    Coral Reef Res Fdn, Box 1765, Koror 96940, Palau.
    Molecular study supports the position of the New Zealand endemic genus Lamellomorpha in the family Vulcanellidae (Porifera, Demospongiae, Tetractinellida), with the description of three new species2019Ingår i: European journal of taxonomy, ISSN 2118-9773, Vol. 506, s. 1-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Due to the possession of huge contort strongyles, and a lack of triaenes in an otherwise 'astrophorine' spicule complement, the phylogenetic position of the endemic, monospecific New Zealand sponge genus, Lamellomorpha Bergquist, 1968, has remained enigmatic. The genus was established within Jaspidae de Laubenfels, 1968 (in the abandoned order Epipolasida Sollas, 1888), but it was not until 2002 that the genus was transferred formally to Astrophorina Sollas, 1887, albeit incertae sedis, by Hooper & Maldonado (2002). In this study, we recognise specimens of Lamellomorpha from the Subantarctic New Zealand region and Chatham Rise, considered by Bergquist to be conspecific with the type species, L. strongylata Bergquist, 1968, first described from the Three Kings-Spirits Bay region of Northland, as the new species, L. australis Kelly & Cardenas sp. nov. These two species of Lamellomorpha have differences in external morphology and colour, skeletal architecture and spicules, natural products, geographical distribution, and depth ranges. Sequencing of the COI Folmer barcode/mini-barcode and of 28S (C1-C2 domains) of these two species suggests phylogenetic affinities of Lamellomorpha with the tetractinellid suborder Astrophorina and the family Vulcanellidae Cardenas et al., 2011. Two Subantarctic New Zealand species of the vulcanellid genus Poecillastra Sollas, 1888, P. ducitriaena Kelly & Cardenas sp. nov. and P. macquariensis Kelly & Cardenas sp. nov., provide further support for the close relationship of Lamellomorpha and Poecillastra.

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  • 62.
    Khalifa, Shaden A. M.
    et al.
    Karolinska Univ Hosp, Clin Res Ctr, Huddinge, Sweden;Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden.
    Elashal, Mohamed
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Menofia Governo, Egypt.
    Kieliszek, Marek
    Warsaw Univ Life Sci SGGW, Fac Food Sci, Dept Biotechnol Microbiol & Food Evaluat, Nowoursynowska 159 C, PL-02776 Warsaw, Poland.
    Ghazala, Naglaa E.
    Agr Res Ctr, Plant Protect Res Inst, Dept Bee Res, Giza 12627, Egypt.
    Farag, Mohamed A.
    Cairo Univ, Coll Pharm, Pharmacognosy Dept, Kasr el Aini St,PB 11562, Cairo, Egypt;Amer Univ Cairo, Sch Sci & Engn, Dept Chem, New Cairo 11835, Egypt.
    Saeed, Aamer
    Quaid I Azam Univ, Islamabad 45320, Pakistan.
    Xiao, Jianbo
    Univ Macau, Inst Chinese Med Sci, Taipa, Macao, Peoples R China;Jiangsu Univ, Coll Food & Biol Engn, Zhenjiang 212013, Peoples R China.
    Zou, Xiaobo
    Jiangsu Univ, Coll Food & Biol Engn, Zhenjiang 212013, Peoples R China.
    Khatib, Alfi
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang, Malaysia;Airlangga Univ, Fac Pharm, Surabaya 60115, Indonesia.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Menofia Governo, Egypt;Al Rayon Coll, Al Rayon Res & Innovat Ctr, Medina 42541, Saudi Arabia;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Peoples R China.
    Recent insights into chemical and pharmacological studies of bee bread2020Ingår i: Trends in Food Science & Technology, ISSN 0924-2244, E-ISSN 1879-3053, Vol. 97, s. 300-316Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Bee bread is a product of the fermentation of a mixture of pollen, nectar and bee saliva that is inoculated by a wide range of bacteria and yeasts necessary for fermentation after storage in comb cells. Bee bread is regarded as the chief protein resource that bees can utilize, especially for feeding of larvae and adults. Since ancient times, bee bread has been used in different cultures for several nutritional and therapeutic purposes. Scope and approach: In this review, we attempt to highlight the possible biological activities, chemical components, methods of isolation and structure of bee bread in addition to its food supplement value and/or medical applications. Key findings and conclusions: Bee bread has been shown to exhibit antimicrobial, antioxidant, antiradical, anticancer, and anti-inflammatory activities. The basic chemical components of bee bread include carbohydrates, proteins and vitamins, as well as minerals, fatty acids and other substances such as enzymes, natural antibiotics, antioxidants and hormones. Bee bread is considered to be a beneficial food supplement. In recent years, there has been significant interest in the use of bee bread to treat many illnesses.

  • 63.
    Khalifa, Shaden A. M.
    et al.
    Karolinska Univ Hosp, Clin Res Ctr, S-14157 Stockholm, Sweden;Stockholm Univ, Dept Mol Biosci, Wenner Gren Inst, SE-10691 Stockholm, Sweden.
    Elias, Nizar
    Univ Kalamoon, Dept Lab Med, Fac Med, POB 222, Dayr Atiyah, Syria.
    Farag, Mohamed A.
    Cairo Univ, Coll Pharm, Pharmacognosy Dept, Kasr El Aini St,PB 11562, Cairo, Egypt;Amer Univ Cairo, Dept Chem, Sch Sci & Engn, New Cairo 11835, Egypt.
    Chen, Lei
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Fujian, Peoples R China.
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chemitry, Islamabad 45320, Pakistan.
    Hegazy, Mohamed-Elamir F.
    Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudingerweg 5, D-55128 Mainz, Germany;Natl Res Ctr, Chem Med Plants Dept, 33 El Bohouth St, Giza 12622, Egypt.
    Moustafa, Moustafa S.
    Kuwait Univ, Dept Chem, Fac Sci, Safat 13060, Kuwait.
    Abd El-Wahed, Aida
    Kuwait Univ, Dept Chem, Fac Sci, Safat 13060, Kuwait.
    Al-Mousawi, Saleh M.
    Kuwait Univ, Dept Chem, Fac Sci, Safat 13060, Kuwait.
    Musharraf, Syed G.
    Univ Karachi, Int Ctr Chem & Biol Sci ICCBS, HEJ Inst Chem Res, Karachi 75270, Pakistan.
    Chang, Fang-Rong
    Kaohsiung Med Univ, Grad Inst Nat Prod, Kaohsiung 807, Taiwan.
    Iwasaki, Arihiro
    Keio Univ, Fac Sci & Technol, Dept Chem, Kohoku Ku, 3-14-1 Hiyoshi, Yokohama, Kanagawa 2238522, Japan.
    Suenaga, Kiyotake
    Keio Univ, Fac Sci & Technol, Dept Chem, Kohoku Ku, 3-14-1 Hiyoshi, Yokohama, Kanagawa 2238522, Japan;Univ HalleWittenberg, Dept Pharmaceut Biol Pharmacognosy, Inst Pharm, Hoher Weg 8, DE-06120 Halle, Saale, Germany.
    Alajlani, Muaaz M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt;Jiangsu Univ, Coll Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China;Al Rayan Coll, Al Rayan Res & Innovat Ctr, Medina 42541, Saudi Arabia.
    Marine Natural Products: A Source of Novel Anticancer Drugs2019Ingår i: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 17, nr 9, artikel-id 491Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.

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  • 64.
    Khalifa, Shaden A. M.
    et al.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden;Karolinska Univ, Karolinska Inst Huddinge, Clin Res Ctr, Dept Lab Med, Solna, Sweden.
    Farag, Mohamed A.
    Cairo Univ, Coll Pharm, Pharmacognosy Dept, Kasr El Aini St, Cairo 11562, Egypt;Amer Univ Cairo, Sch Sci & Engn, Dept Chem, New Cairo 11835, Egypt.
    Yosri, Nermeen
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.
    Sabir, Jamal S. M.
    KAU, Ctr Excellence Bionosci Res, Jeddah 21589, Saudi Arabia;KAU, Fac Sci, Dept Biol Sci, Biotechnol Res Grp, Jeddah 21589, Saudi Arabia.
    Saeed, Aamer
    Quaid I Azam Univ, Islamabad 45320, Pakistan.
    Al-Mousawi, Saleh Mohammed
    Univ Kuwait, Fac Sci, Dept Chem, POB 5969, Safat 13060, Kuwait;Univ Karachi, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    Taha, Wafaa
    Minist Hlth, Reg Colab, Pesticides Residues Food & Water Dept, Menoufia, Egypt.
    Musharraf, Syed Ghulam
    Patel, Seema
    San Diego State Univ, Bioinformat & Med Informat Res Ctr, San Diego, CA 92182 USA.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt;Al Rayon Coll, Al Rayon Res & Innovat Ctr, Medina 42541, Saudi Arabia;Jiangsu Univ, Coll Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China.
    Truffles: From Islamic culture to chemistry, pharmacology, and food trends in recent times2019Ingår i: Trends in Food Science & Technology, ISSN 0924-2244, E-ISSN 1879-3053, Vol. 91, s. 193-218Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Many years back, during Islamic civilization, truffle (Kama'ah) was mentioned by Prophet Muhammed (PBUH) to be well recognized as a therapeutic for eye diseases. ("In the Sahihain, it is narrated that the Prophet said: "The Kama'ah (truffle) is among the manna (which is a food mentioned in the Qura'n, Surah alBagarah), and its water (extract or juice) cures the eye diseases"). Truffles represent a large group of soil fungi belonging to Ascomycota, Basidiomycota, and Zygomycota. Because of their exceptionally profitable protein, fat, polysaccharide, carbohydrate, ash, mineral, phenolic and other organic molecule contents, truffles have been appreciated as food, nutritional and therapeutic sources for many years. Scope and approach: The main aim of this review is to highlight a comprehensive compile of truffles traditional uses, mycochemistry, pharmacological properties and nutritional value with special focus on desert truffles. Such review represents a good candidate reference for future truffle research. Key findings and conclusions: In this review, we discuss the traditional aspects of truffles with reference to Prophetic Traditional Medicine (al-Tibb al-Nabawi) to cure aliments such as trachoma. The use of truffles is justified by many recent research findings with regards to their anti-inflammatory, anti-bacterial, anti-oxidant, and anti-cancer properties. Although the molecular mechanism and functions of the different truffle species have been intensively studied, we look forward to translating these traditional remedies into preclinical and clinical applications.

  • 65.
    Lai, K. H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
    Lu, M. C.
    Natl Dong Hwa Univ, Grad Inst Marine Biotechnol, Pingtung 944, Taiwan.;Natl Museum Marine Biol & Aquarium, Pingtung 944, Taiwan..
    Chang, F. R.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan.;Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung 80708, Taiwan.;Kaohsiung Med Univ, Res Ctr Nat Prod & New Drug, Kaohsiung 80708, Taiwan..
    Su, J. H.
    Natl Dong Hwa Univ, Grad Inst Marine Biotechnol, Pingtung 944, Taiwan.;Natl Museum Marine Biol & Aquarium, Pingtung 944, Taiwan..
    El-Shazly, M.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan.;Ain Shams Univ, Fac Pharm, Dept Pharmacognosy & Nat Prod Chem, Org African Unity St, Cairo 11566, Egypt..
    Du, Y. C.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan..
    Wu, T. Y.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan..
    Hsu, Y. M.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan..
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Wu, Y. C.
    Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807, Taiwan.;China Med Univ, Sch Pharm, Coll Pharm, Taichung 40402, Taiwan.;China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung 40447, Taiwan.;China Med Univ Hosp, Ctr Mol Med, Taichung 40447, Taiwan..
    Antileukemic sesterterpenoids from a marine sponge, Luffariella sp.2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Artikel i tidskrift (Övrigt vetenskapligt)
  • 66.
    Liu, Xiaojie
    et al.
    Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands..
    Ahlgren, Samantha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands.
    Korthout, Henrie A. A. J.
    Fytagoras BV, NL-2333 BE Leiden, Netherlands..
    Salome-Abarca, Luis F.
    Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands..
    Bayona, Lina M.
    Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands..
    Verpoorte, Robert
    Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands..
    Choi, Young Hae
    Leiden Univ, Inst Biol, Nat Prod Lab, NL-2333 BE Leiden, Netherlands.;Kyung Hee Univ, Coll Pharm, Seoul 02447, South Korea..
    Broad range chemical profiling of natural deep eutectic solvent extracts using a high performance thin layer chromatography-based method2018Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1532, s. 198-207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natural deep eutectic solvents (NADES) made mainly with abundant primary metabolites are being increasingly applied in green chemistry. The advantages of NADES as green solvents have led to their use in novel green products for the food, cosmetics and pharma markets. However, one of the main difficulties encountered in the development of novel products and their quality control arises from their low vapour pressure and high viscosity. These features create the need for the development of new analytical methods suited to this type of sample. In this study, such a method was developed and applied to analyse the efficiency of a diverse set of NADES for the extraction of compounds of interest from two model plants, Ginkgo biloba and Panax ginseng. The method uses high-performance thin-layer chromatography (HPTLC) coupled with multivariate data analysis (MVDA). It was successfully applied to the comparative quali- and quantitative analysis of very chemically diverse metabolites (e.g., phenolics, terpenoids, phenolic acids and saponins) that are present in the extracts obtained from the plants using six different NADES. The composition of each NADES was a combination of two or three compounds mixed in defined molar ratios; malic acid-choline chloride (1:1), malic acid-glucose (1:1), choline chloride-glucose (5:2), malic acid-proline (1:1), glucose-fructose-sucrose (1:1:1) and glycerol-proline-sucrose (9:4:1). Of these mixtures, malic acid-choline chloride (1:1) and glycerol-proline-sucrose (1:1:1) for G. biloba leaves, and malic acid-choline chloride (1:1) and malic acid-glucose (1:1) for P. ginseng leaves and stems showed the highest yields of the target compounds. Interestingly, none of the NADES extracted ginkgolic acids as much as the conventional organic solvents. As these compounds are considered to be toxic, the fact that these NADES produce virtually ginkgolic acid-free extracts is extremely useful. The effect of adding different volumes of water to the most efficient NADES was also evaluated and the results revealed that there is a great influence exerted by the water content, with maximum yields of ginkgolides, phenolics and ginsenosides being obtained with approximately 20% water (w/w).

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  • 67.
    Liu, Xiaoyan
    et al.
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Liu, Dan
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Chen, Yihan
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Zhong, Ruting
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Gao, Luying
    Nanjing Med Univ, Nanjing Hosp 1, Dept Pediat, Nanjing 210006, Peoples R China.
    Yang, Chengfeng
    China Agr Univ, Coll Food Sci & Nutr Engn, Beijing 100083, Peoples R China.
    Ai, Chao
    South China Univ Technol, Sch Food Sci & Engn, Guangzhou 510641, Peoples R China.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Al Rayan Coll, Al Rayan Res & Innovat Ctr, Medina 42541, Saudi Arabia;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Zhejiang, Peoples R China.
    Zhao, Chao
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China;Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Physicochemical characterization of a polysaccharide from Agrocybe aegirita and its anti-ageing activity2020Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 236, artikel-id 116056Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study is to characterize the structure of a novel natural polysaccharide from Agrocybe aegirita (AAPS) and evaluate its anti-aging activity. The MALLS and GC-MS analysis indicated that the AAPS with molecular weights of 1.81 x 10(4) Da was mainly composed by rhamnose, fucose, mannose, and glucose in a molar ratio of 2.90:10.25:3.70:38.27. The FT-IR and NMR analysis showed that the backbone of AAPS was alpha-L-Rhap-(1 -> 6)-beta-D-Glcp-(1 -> 2)-alpha-L-Fucp-(1 -> 6)-alpha-D-Glcp-(1 -> 5)-alpha-L-Araf-(1 -> 4)-beta-D-GlcpA-(1 -> 5)-alpha-L-Araf-(1 -> 6)-alpha-D-Manp-(1 -> 6)-alpha-D-Manp-(1 -> 2)-alpha-L-Fucp-(1 -> 6)-beta-D-Glap-(1 -> 2)-alpha-L-Rhap-(1 -> 6)-beta-D-Galp-(1 -> which linked with two side chains alpha-L-Fucp-(1 -> 6)-beta-D-Glcp-(1 -> 6)-beta-D-Manp-(1 -> and alpha-D-Xylp-(1 -> 2)-alpha-L-Fucp-(1 -> 5) -alpha-D-Araf-(1.6)-beta-D-Galp-(1 -> at O-H2 at H-4-arabinose and the terminal Galp residues, respectively. The MRC-5 cells induced by H2O2 were used to explore the anti-ageing effect and its underlying mechanism of AAPS. It showed a potent anti-ageing activity, representing by the increased cell viability and beta-Gal viability, prevented G1-phase cell-cycle arrest, and decreased mitochondrial membrane potential. The polysaccharides extracted from A. aegirita might be applied in functional food as anti-ageing ingredient.

  • 68.
    Liu, Xiao-yan
    et al.
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China;China Agr Univ, Coll Food Sci & Nutr Engn, Beijing 100083, Peoples R China.
    Liu, Dan
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Lin, Guo-peng
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.
    Wu, Yi-jing
    Minjiang Univ, Inst Oceanog, Fuzhou 350108, Peoples R China.
    Gao, Lu-ying
    Nanjing Med Univ, Nanjing Hosp 1, Dept Pediat, Nanjing 210006, Peoples R China.
    Ai, Chao
    South China Univ Technol, Sch Food Sci & Engn, Guangzhou 510641, Peoples R China.
    Huang, Yi-fan
    Fujian Agr & Forestry Univ, Coll Anim Sci, Fuzhou 350002, Peoples R China.
    Wang, Ming-fu
    Providence Univ, Food & Nutr Dept, Taichung 43301, Taiwan.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Chen, Xin-hua
    Fujian Agr & Forestry Univ, Inst Oceanol, Key Lab Marine Biotechnol Fujian Prov, Fuzhou 350002, Peoples R China.
    Zhao, Chao
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China;Univ Macau, State Key Lab Qual Control Chinese Med, Inst Chinese Med Sci, Taipa, Macau, Peoples R China.
    Anti-ageing and antioxidant effects of sulfate oligosaccharides from green algae Ulva lactuca and Enteromorpha prolifera in SAMP8 mice2019Ingår i: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 139, s. 342-351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oligosaccharides from green algae Ulva lactuca (ULO) and Enteromorpha prolifera (EPO) were used for investigation of anti-ageing effects and the underlying mechanism in SAMP8 mice. The structural properties of ULO and EPO were analyzed by fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and agarose gel electrophoresis. These oligosaccharides enhanced the glutathione, superoxide dismutase, catalase, and telomerase levels and total antioxidant capicity, and decreased the levels of malondialdehyde and advanced glycation end products. After ULO and EPO treatment, the levels of inflammatory factors, including IFN-gamma, TNF-alpha, and IL-6, decreased; the BDNF and ChAT levels increased; and hippocampal neurons were protected. Downregulation of the p53 and FOXO1 genes and upregulation of the Sirt1 gene indicated that ULO and EPO have potential therapeutic effects in the prevention of ageing in SAMP8 mice. By 16S rRNA gene high-throughput sequencing, the abundance of Desulfovibrio was discovered to be markedly different in mice treated with ULO and EPO. The abundances of Verrucomicrobiaceae, Odoribacteraceae, Mogibacteriaceae, Planococcaceae, and Coriobacteriaceae were positively correlated with age-related indicators. These results demonstrated that oligosaccharides from U. lactuca and E. prolifera are ideal candidate compounds that can be used in functional foods and pharmaceuticals to prevent ageing. 

  • 69.
    Love, Gordon D.
    et al.
    Univ Calif Riverside, Dept Earth & Planetary Sci, Riverside, CA 92521 USA.
    Zumberge, J. Alex
    Univ Calif Riverside, Dept Earth & Planetary Sci, Riverside, CA 92521 USA.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Sperling, Erik A.
    Stanford Univ, Dept Geol Sci, Stanford, CA 94305 USA.
    Rohrssen, Megan
    Cent Michigan Univ, Dept Earth & Atmospher Sci, Mt Pleasant, MI 48859 USA.
    Grosjean, Emmanuelle
    Geosci Australia, Canberra, ACT, Australia.
    Grotzinger, John P.
    CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
    Summons, Roger E.
    MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA USA.
    Sources of C30 steroid biomarkers in Neoproterozoic-Cambrian rocks and oils2020Ingår i: Nature Ecology & Evolution, E-ISSN 2397-334X, Vol. 4, nr 1, s. 34-36Artikel i tidskrift (Övrigt vetenskapligt)
  • 70.
    Luis Carballo, Jose
    et al.
    Univ Nacl Autonoma Mexico, Inst Ciencias Mar & Limnol, Unidad Acad Mazatlan, Ave Joel Montes Camarena S-N,POB 811, Mazatlan 82000, Sin, Mexico.
    Bautista-Guerrero, Eric
    Univ Guadalajara, Ctr Invest Costeras, Ctr Univ Costa, Lab Ecol Marina, Ave Univ 2013 Del, Puerto Vallarta 48280, Jalisco, Mexico.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Antonio Cruz-Barraza, Jose
    Univ Nacl Autonoma Mexico, Inst Ciencias Mar & Limnol, Unidad Acad Mazatlan, Ave Joel Montes Camarena S-N,POB 811, Mazatlan 82000, Sin, Mexico.
    Maria Aguilar-Camacho, Jose
    Natl Univ Ireland Galway, Sch Nat, Sci, Zool,Ryan Inst, Univ Rd, Galway, Ireland.
    Molecular and morphological data from Thoosidae in favour of the creation of a new suborder of Tetractinellida2018Ingår i: Systematics and Biodiversity, ISSN 1477-2000, E-ISSN 1478-0933, Vol. 16, nr 5, s. 512-521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Thoosidae (Porifera, Demospongiae, Tetractinellida) currently includes the genera Thoosa, Alectona, and Delectona. To this date, molecular data are only available for Alectona. In this study, the phylogenetic affinities of the genera Thoosa and Alectona have been investigated with the species T. mismalolli, T. calpulli, and T. purpurea from the Mexican Pacific using morphology and three molecular loci: the mitochondrial cytochrome oxidase subunit 1 (CO1 mtDNA), 28S rRNA (fragment D2), and 18S rRNA. Morphology and embryology showed that these genera are quite different from the rest of the tetractinellids because larvae of Alectona and Thoosa have unique features in sponges, such as the presence of monaxonic discs in Thoosa and tetraxonic discs in Alectona which disappear in the adult stages. A phylogenetic analysis using selected species from the order Tetractinellida revealed that Thoosa groups with Alectona thus confirming morphological studies. The peculiarities in spiculation and embryology of the Thoosa and Alectona larvae, which are markedly different from species belonging to the suborders Astrophorina and Spirophorina and their distant phylogenetic position (based on three molecular loci), suggest that Thoosidae could be placed in the new suborder Thoosina.

  • 71.
    Miao, Lingchao
    et al.
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Tao, Hongxun
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Peng, Yu
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Wang, Shengpeng
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Zhong, Zhangfeng
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Dragan, Simona
    Univ Med & Farm Timisoara, 2 Eftimie Murgu Sq, Timisoara 300041, Romania.
    Zengin, Gokhan
    Selcuk Univ, Sci Fac, Dept Biol, Konya, Turkey.
    Cheang, Wai San
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Wang, Yitao
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    Xiao, Jianbo
    Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China.
    The anti-inflammatory potential of Portulaca oleracea L. (purslane) extract by partial suppression on NF-kappa B and MAPK activation2019Ingår i: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 290, s. 239-245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Portulaca oleracea L. (Purslane) has great potential as food and traditional drugs in several countries. The purpose of this study was to evaluate the anti-inflammatory effects of purslane extract on lipopolysaccharide (LPS)stimulated RAW 264.7 cells. Purslane extracts significantly reduced LPS-induced synthesis of NO in a dose-dependent manner, as well as the expression levels of iNOS and COX-2. The productions of TNF-alpha and IL-6 were also significantly reduced at the higher dose of 400 mu g/ml. Meanwhile, the expression levels of P65, p-P65, p-MEK and p-I kappa B-alpha were inhibited dose-dependently. The nuclear translocation of P65 was partially prevented by the extract, which explained the inhibition of NF-kappa B pathway. In addition, three reported flavonoids, named luteolin, kaempferol and quercitrin, were identified in the extract, which might be responsible for its anti-inflammatory effects. Above all, our research has partially proved that purslane could be considered as a natural anti-inflammatory agent in further applications.

  • 72.
    Mohotti, S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Colombo, Fac Sci, Dept Chem, Thurstan Rd, Colombo 00300, Sri Lanka..
    Rajendran, S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Muhammad, Taj
    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.
    Burman, R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Hellman, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    de Silva, E. D.
    Univ Colombo, Fac Sci, Dept Chem, Thurstan Rd, Colombo 00300, Sri Lanka..
    Goransson, U.
    Univ Colombo, Fac Sci, Dept Chem, Thurstan Rd, Colombo 00300, Sri Lanka..
    Hettiarachchi, C. M.
    Univ Colombo, Fac Sci, Dept Chem, Thurstan Rd, Colombo 00300, Sri Lanka..
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    A bioactivity-guided screening of Sri Lankan plants in the search for novel antibacterial and anticancer agents2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Artikel i tidskrift (Övrigt vetenskapligt)
  • 73.
    Mohotti, Supun
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Colombo, Dept Chem, Fac Sci, Thurston Rd, Colombo 03, Sri Lanka.
    Rajendran, Sanjeevan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Colombo, Dept Chem, Fac Sci, Thurston Rd, Colombo 03, Sri Lanka.
    Muhammad, Taj
    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.
    Adhikari, Achyut
    Tribhuvan Univ, Cent Dept Chem, Kathmandu, Nepal.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    de Silva, E. D.
    Univ Colombo, Dept Chem, Fac Sci, Thurston Rd, Colombo 03, Sri Lanka.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Hettiarachchi, C. M.
    Univ Colombo, Dept Chem, Fac Sci, Thurston Rd, Colombo 03, Sri Lanka.
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Screening for bioactive secondary metabolites in Sri Lankan medicinal plants by microfractionation and targeted isolation of antimicrobial flavonoids from Derris scandens2019Ingår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 246, artikel-id 112158Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ethnopharmacological relevance: Sri Lanka is known to have very diverse flora. Many of these species are used for plant-based remedies, which form the integral part of two Sri Lankan systems of traditional medicine, Ayurveda and Deshiya Chikitsa. Despite their widespread use, only a limited number of studies have probed into the scientific evidence for bioactivity of these medicinal plants. Such studies rarely progress to the identification of bioactive natural products. Aim of the study: The primary aim was to develop a bioactivity screening method and apply it to 50 Sri Lankan medicinal plants where antimicrobial properties could be relevant for its traditional use. The subsequent aim was the progression into defining and characterising potent isolates within targeted compound classes from such plants, i.e. Derris scandens and its antimicrobial flavonoids. Material and methods: The plant collection comprised 24 species of Fabaceae, 15 Rubiaceae, 7 Solanaceae and 4 Cucurbitaceae plants. These 50 species were collected based on their ethnopharmacological importance and use in Sri Lankan traditional medicine. Crude extracts from each species were initially subjected to radial disc diffusion and microdilution assays. Subsequently, aqueous extracts of all plants were microfractionated in deep well plates using reversed-phase HPLC. Fractions were tested for antibacterial and cytotoxic activities and masses of target bioactive compounds were identified using mass spectrometry. Bioactive compounds with the masses identified through microfractions were isolated from Derris scandens using reversed-phase HPLC. The isolated pure compounds were characterised using LC-MS and NMR. Results: Crude aqueous extracts from 19 species showed activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) in the radial disc diffusion assay. Crude aqueous extracts from 34 plant species and organic extracts from 46 plant species were active against S. aureus (<= 4 mg mL(-1)) in the microdilution assay. Microfractionation demonstrated antibacterial activity for 19 plants and cytotoxicity for 6 plants. Furthermore, target bioactive compounds and their molecular ions were identified during microfractionation. Dalpanitin and vicenin-3, two of the flavonoids isolated from Derris scandens gave MICs of 23 mu g mL(-1) against S. aureus. Dalpanitin also exhibited relevant MICs on Gram-negative bacteria (94 mu g mL(-1)) against Escherichia coli and Pseudomonas aeruginosa). Conclusion: The microfractionation protocol developed in this study enabled time-efficient screening of many plants species, using a small quantity of sample material. In addition, microfractionation served as a guiding tool for identifying individual antimicrobial compounds. Through this process, flavonoids were isolated from Derris scandens, out of which dalpanitin and vicenin-3 showed activity in the low micromolar range. The high hit rate for in vitro antibacterial properties from this ethnopharmacologically guided sample collection gives credence to Sri Lankan traditional herbal medicine as a source for drug discovery.

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  • 74.
    Morrow, Christine
    et al.
    Natl Univ Ireland Galway, Sch Nat Sci, Univ Rd, Galway, Ireland;Natl Univ Ireland Galway, Ryan Inst, Univ Rd, Galway, Ireland;Queens Univ, Marine Lab, 12-13 Strand, Portaferry, North Ireland;Natl Museums Northern Ireland, 153 Bangor Rd, Holywood BT18 0EU, North Ireland.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Boury-Esnault, Nicole
    Univ Avignon, Aix Marseille Univ, CNRS, IMBE,IRD,Stn Marine Endoume, F-13007 Marseille, France.
    Picton, Bernard
    Natl Museums Northern Ireland, 153 Bangor Rd, Holywood BT18 0EU, North Ireland.
    Mccormack, Grace
    Natl Univ Ireland Galway, Sch Nat Sci, Univ Rd, Galway, Ireland;Natl Univ Ireland Galway, Ryan Inst, Univ Rd, Galway, Ireland.
    Van Soest, Rob
    Netherlands Ctr Biodivers Naturalis, Leiden, Netherlands.
    Collins, Allen
    Smithsonian Inst, Natl Museum Nat Hist, Natl Systemat Lab, MRC 153,POB 37012, Washington, DC 20013 USA.
    Redmond, Niamh
    Smithsonian Inst, Natl Museum Nat Hist, DNA Barcode Network, MRC 183,POB 37012, Washington, DC 20013 USA.
    Maggs, Christine
    Joint Nat Conservat Comm, Monkstone House,City Rd, Peterborough PE1 1JY, Cambs, England.
    Sigwart, Julia
    Queens Univ, Marine Lab, 12-13 Strand, Portaferry, North Ireland.
    Allcock, Louise A.
    Natl Univ Ireland Galway, Sch Nat Sci, Univ Rd, Galway, Ireland;Natl Univ Ireland Galway, Ryan Inst, Univ Rd, Galway, Ireland.
    Integrating morphological and molecular taxonomy with the revised concept of Stelligeridae (Porifera: Demospongiae)2019Ingår i: Zoological Journal of the Linnean Society, ISSN 0024-4082, E-ISSN 1096-3642, Vol. 187, nr 1, s. 31-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study reinforces and extends the findings of previous molecular studies showing that there is a dose relationship between species assigned to the sponge genera Halicnemia, Higginsia, Paratimea and Stelligera and that the family Heteroxyidae is polyphyletic. The present study has led to the description of one new species of Halicnemia and six new species of Paratimea, the resurrection of Halicnemia gallica and a better understanding of the characters uniting Stelligeridae. A new species of Heteroxya is also described. We demonstrate that many of the taxa assigned to Heteroxyidae are more closely related to other families, and we propose several changes to the classification of Heteroscleromorpha. Desmoxyidae is resurrected from synonymy and transferred to Poecilosclerida; Higginsia anfractuosa is transferred to Hymedesmiidae, and a new genus, Hooperia, is erected for its reception; Higginsia durissima is returned to Bubaris (Bubaridae); Higginsia fragilis is transferred to Spanioplon (Hymedesmiidae); Hemiasterella camelus is transferred to Paratimea; and Raspailia (Parasyringella) australiensis and Ceratopsion axiferum are transferred to Adreus (Hemiasterellidae).

  • 75.
    Moustafa, Moustafa Sherief
    et al.
    Univ Kuwait, Dept Chem, Fac Sci, POB 5969, Safat 13060, Kuwait.
    Al-Mousawi, Saleh Mohammed
    Univ Kuwait, Dept Chem, Fac Sci, POB 5969, Safat 13060, Kuwait.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Karachi, Res Inst Chem, ICCBS, Karachi 75270, Pakistan;Menoufia Univ, Chem Dept, Fac Sci, Menoufia, Egypt.
    Elnagdi, Mohamed Hilmy
    Cairo Univ, Dept Chem, Fac Sci, POB 12613, Giza, Egypt.
    Chemistry of Heterocyclic Five and Six Membered Enamino Nitriles and Enamino Esters2018Ingår i: Mini-Reviews in medical chemistry, ISSN 1389-5575, E-ISSN 1875-5607, Vol. 18, nr 12, s. 992-1007Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Progress in the chemistry of cyclic enamino-nitriles based on the advanced synthetic methodologies is reported. Due to the recent accomplishment, it becomes possible to reactivate these molecules toward electrophiles, nucleophiles and as electron rich dienes in 2+3 dipolar additions and in 4+2 cycloadditions reactions. Synthesizing the poly functionalized 4H-pyrans and their fused derivatives is a fascinating field with a multitude of biological implications such as antitumor, cardiotonic, hepatoprotective, antihypertensive, antibronchitis, as well antifungal activity. This work was conducted with particular emphasis on reviewing the work done on the cyclic enamines since 1990 up till now in order to highlight in more details the synthetic pathways, interactions and the biological activities, Furthermore; we referred to the recent original data of our group contributions within this field.

  • 76.
    Moustafa, Moustafa Sherief
    et al.
    Univ Kuwait, Fac Sci, Dept Chem, Safat Kuwait, Kuwait.
    Al-Mousawi, Saleh Mohammed
    Univ Kuwait, Fac Sci, Dept Chem, Safat Kuwait, Kuwait.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Elnagdi, Mohamed Hilmy
    Cairo Univ, Fac Sci, Dept Chem, Giza, Egypt.
    Tales of the Unexpected in Synthesis of Polyfunctional Heteroaromatics2018Ingår i: Current Organic Synthesis, ISSN 1570-1794, E-ISSN 1875-6271, Vol. 15, nr 5, s. 587-602Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Our research group has a longstanding interest in the synthesis of novel functionalized heteroaromatic compounds, and the development of new methods for this purpose. During our ongoing investigations, we recently had an instance to check the reproducibility of some published results concerning the chemistry of arylhydrazonals, enamines and other functionally substituted carbonyl compounds. This work has led to the discovery of some new rearrangements, and the revision of the structures originally assigned to several molecules.

    Objective: This review surveys some correction of several erroneous reports that have appeared in the literature, and presents some interesting new rearrangements discovered in the course of investigating older reports.

    Results: The crystallographic studies revealed that the condensation of arylhydrazonals with active methylenenitriles yields arylazoniconates rather than pyridazenones as previously reported. Additionally, phenathylthiocyanate reacts with malononitrile to afford thiazoles rather than the previously reported condensation with the carbonyl group. In another example, the reaction of phenethylmalononitrile with hydrazine yields pyrazolopyridazenes rather than phenacylpyrazol-3,5-diamine. In yet another case, several interesting Dimrothtype rearrangements were observed when malononitrile was condensed with enaminones, contradicting earlier reports. Unexpectedly, these enaminones underwent self-trimerization to yield 1,3,5-trisubstituted benzenes under certain conditions. Enaminonitriles also undergo interesting and novel Dimroth rearrangements when reacted with cyclohexanedione or dehydroacetic acid derivatives.

    Conclusion: We have shown that the structures of several complex heterocyclic compounds that have been reported in the literature over the last 50 years were incorrectly assigned, possibly because the authors who originally reported them were using substandard or outdated analytical equipments.

  • 77.
    Muhammad, Taj
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    LL-37-derived cyclic antimicrobial drug leads: Design, synthesis, activity and different ways of creating them 2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In an era where last-line antibiotics are failing, one of the powerful approaches to develop novel therapeutic agents is to turn back to nature in order to identify possible drug candidates. Among the potential candidates, antimicrobial peptides (AMPs) have garnered much attention as an antimicrobial. These are broad spectrum host defense molecules produced by all living organisms. LL-37 is such a multitask human defense peptide that mediates various host immune responses and also exerts antimicrobial activity. However, the direct use of this 37-amino acid long α-helical peptide is hampered by protease susceptibility, in particular for antimicrobial applications. A small 12-residues peptide, referred as KR-12, derived from LL-37, has been reported to have selective toxic effect on bacteria. 

    Analogues of KR-12 were generated in the form of Alanine and Lysine scans to find out the positions important for improved activity and selectivity. Backbone-cyclised dimers based on KR-12 and KR-12 analogues, tethered by linkers of two to four amino acid residues, were synthesised to explore the concept of cyclisation, dimerisation and cross-linking as means to enhance peptide stability and activity. Antimicrobial activities of the linear peptides and cyclic dimers were assayed against human pathogens, in buffer and/or physiological conditions. Proteolytic stability, permeabilisation efficacy on microbial membranes and, their structures were also characterised.  

    From Ala and Lys scans, it was possible to identify two key positions for the enhanced broad-spectrum antibacterial activity: replacement of Gln5 with Lys, and Asp9 with either Ala or Lys. In serum stability assay, KR-12 and analogues were found to be unstable. The backbone-cyclised KR-12 dimers showed improved antimicrobial activity and increased stability compared to monomeric KR-12. KR-12 monomers adopt a well-defined α-helical structure in membrane-mimicking environment, while cyclised dimers were unstructured in solution judged by NMR. The KR-12 (Q5K, D9A) cyclised dimers retained antimicrobial activity in physiological conditions. Circular dichroism showed that the cyclic dimer, cd4-PP, had 77% helical content when bound to lyso-phosphatidylglycerol micelles.

    Moreover, the limits of cyanobactin-macrocyclase PatGmac were explored to cyclise peptides larger than their natural substrates, namely the PawS derived peptide Sunflower Trypsin Inhibitor-1 (SFTI-1) and the cyclotide kalata B1. PatGmac was used very efficiently to cyclise SFTI-1. In addition, semi-pure butelase 1, isolated from Clitoria ternatea seeds, was immobilised on NHS column. The immobilised column was then used to produce substrates ranging from 16 to 34 varying length.

    Delarbeten
    1. Alanine and Lysine Scans of the LL-37-Derived Peptide Fragment KR-12 Reveal Key Residues for Antimicrobial Activity
    Öppna denna publikation i ny flik eller fönster >>Alanine and Lysine Scans of the LL-37-Derived Peptide Fragment KR-12 Reveal Key Residues for Antimicrobial Activity
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    2018 (Engelska)Ingår i: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 19, nr 9, s. 931-939Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The human host defence peptide LL-37 is a broad-spectrum antibiotic with immunomodulatory functions. Residues 18-29 in LL-37 have previously been identified as a minimal peptide (KR-12) that retains antibacterial activity with decreased cytotoxicity. In this study, analogues of KR-12 were generated by Ala and Lys scans to identify key elements for activity. These were tested against a panel of human pathogens and for membrane permeabilisation on liposomes. Replacements of hydrophobic and cationic residues with Ala were detrimental for antibiotic potency. Substitutions by Lys increased activity, as long as the increase in cationic density did not disrupt the amphiphilic disposition of the helical structure. Importantly, substitutions showed differential effects against different organisms. Replacement of Gln5 with Lys and Asp9 with Ala or Lys improved the broad-spectrum activity most, each resulting in up to an eightfold increase in potency against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. The improved analogues displayed no significant toxicity against human cells, and thus, KR-12 is a tuneable template for antibiotic development.

    Ort, förlag, år, upplaga, sidor
    WILEY-V C H VERLAG GMBH, 2018
    Nyckelord
    antibiotics, cytotoxicity, drug discovery, peptides, structure-activity relationships
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-356391 (URN)10.1002/cbic.201700599 (DOI)000431625100008 ()29430821 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2011-3403Carl Tryggers stiftelse för vetenskaplig forskning , CTS 10: 126Carl Tryggers stiftelse för vetenskaplig forskning , CTS 11: 169Svenska läkaresällskapet, SLS-254511
    Tillgänglig från: 2018-07-25 Skapad: 2018-07-25 Senast uppdaterad: 2020-02-18Bibliografiskt granskad
    2. Backbone cyclisation and dimerisation of LL-37-derived peptides enhance antimicrobial activity and proteolytic stability
    Öppna denna publikation i ny flik eller fönster >>Backbone cyclisation and dimerisation of LL-37-derived peptides enhance antimicrobial activity and proteolytic stability
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    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-397022 (URN)
    Tillgänglig från: 2019-11-13 Skapad: 2019-11-13 Senast uppdaterad: 2019-11-18
    3. Transformation of KR-12 derived cross-linked cyclic dimers into stable and potent antimicrobial drug leads
    Öppna denna publikation i ny flik eller fönster >>Transformation of KR-12 derived cross-linked cyclic dimers into stable and potent antimicrobial drug leads
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-397187 (URN)
    Tillgänglig från: 2019-11-18 Skapad: 2019-11-18 Senast uppdaterad: 2019-11-18
    4. Exploring the limits of cyanobactin macrocyclase PatGmac: Cyclisation of PawS derived peptide sunflower trypsin inhibitor-1 and cyclotide kalata B1
    Öppna denna publikation i ny flik eller fönster >>Exploring the limits of cyanobactin macrocyclase PatGmac: Cyclisation of PawS derived peptide sunflower trypsin inhibitor-1 and cyclotide kalata B1
    Visa övriga...
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-397023 (URN)
    Tillgänglig från: 2019-11-13 Skapad: 2019-11-13 Senast uppdaterad: 2019-11-18
    5. Immobilisation of semi-pure butelase 1 and its applications to produce head-to-tail cyclic peptides
    Öppna denna publikation i ny flik eller fönster >>Immobilisation of semi-pure butelase 1 and its applications to produce head-to-tail cyclic peptides
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Farmakognosi
    Identifikatorer
    urn:nbn:se:uu:diva-397188 (URN)
    Tillgänglig från: 2019-11-18 Skapad: 2019-11-18 Senast uppdaterad: 2019-11-18
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  • 78.
    Muhammad, Taj
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Gunasekera, Sunithi
    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.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Engineering of KR-12: A minimalized domain derived from human host defense peptide LL-37 into a potent antimicrobial drug lead2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Artikel i tidskrift (Övrigt vetenskapligt)
  • 79.
    Muhammad, Taj
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Houssen, E. Wael
    Department of Chemistry, Marine Biodiscovery Centre, University of Aberdeen, Aberdeen AB243UE, Scotland, UK..
    Thomas, Louise
    Department of Chemistry, Marine Biodiscovery Centre, University of Aberdeen, Aberdeen AB243UE, Scotland, UK..
    Alexandru-Crivac, Cristina-Nicoleta
    Centre, University of Aberdeen, Aberdeen AB243UE, Scotland, UK..
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Jaspars, Marcel
    Centre, University of Aberdeen, Aberdeen AB243UE, Scotland, UK..
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Exploring the limits of cyanobactin macrocyclase PatGmac: Cyclisation of PawS derived peptide sunflower trypsin inhibitor-1 and cyclotide kalata B1Ingår i: Artikel i tidskrift (Refereegranskat)
  • 80.
    Muhammad, Taj
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Shafiullah, Md.
    Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Uppsala, Sweden.
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Immobilisation of semi-pure butelase 1 and its applications to produce head-to-tail cyclic peptidesManuskript (preprint) (Övrigt vetenskapligt)
  • 81.
    Muhammad, Taj
    et al.
    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.
    Skogman, Malena
    Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Fallarero, Adyary
    Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Transformation of KR-12 derived cross-linked cyclic dimers into stable and potent antimicrobial drug leadsManuskript (preprint) (Övrigt vetenskapligt)
  • 82.
    Murugesu, Suganya
    et al.
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Ibrahim, Zalikha
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Ahmed, Qamar-Uddin
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Yusoff, Nik-Idris Nik
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Uzir, Bisha-Fathamah
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Perumal, Vikneswari
    Univ Kuala Lumpur, Royal Coll Med Perak, Fac Pharm & Hlth Sci, Ipoh 30450, Perak Darul Rid, Malaysia.
    Abas, Faridah
    Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    Saari, Khozirah
    Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    Khatib, Alfi
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia;Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    Characterization of alpha-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation2018Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 9, artikel-id 2402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the alpha-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their alpha-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential alpha-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.

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  • 83.
    Murugesu, Suganya
    et al.
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia;Univ Kuala Lumpur, Fac Pharm & Hlth Sci, Perak Darul Ridzuan, Royal Coll Med Perak, Ipoh 30450, Perak Darul Rid, Malaysia.
    Khatib, Alfi
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia;Univ Malaysia, Int Islamic, Kulliyyah Sci, Cent Res & Anim Facil, Kuantan 25200, Pahang Darul Ma, Malaysia;Airlangga Univ, Fac Pharm, Surabaya 60155, Indonesia.
    Ahmed, Qamar Uddin
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia.
    Ibrahim, Zalikha
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia.
    Uzir, Bisha Fathamah
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia.
    Benchoula, Khaled
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia.
    Yusoff, Nik Idris Nik
    Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kulliyyah Pharm, Pharmacognosy Res Grp, Kuantan, Pahang Darul Ma, Malaysia.
    Perumal, Vikneswari
    Univ Kuala Lumpur, Fac Pharm & Hlth Sci, Perak Darul Ridzuan, Royal Coll Med Perak, Ipoh 30450, Perak Darul Rid, Malaysia.
    Alajmi, Mohamed F.
    King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh 11451, Saudi Arabia.
    Salamah, Sahal
    King Saud Bin Abdul Aziz Univ Hlth Sci, Jeddah 21423, Saudi Arabia.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Al Rayan Coll, Al Rayan Res & Innovat Ctr, Medina 42541, Saudi Arabia;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.
    Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos2019Ingår i: Toxicology reports, ISSN 1972-6325, E-ISSN 2214-7500, Vol. 6, s. 1148-1154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows nontoxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 mu g/ml, 31.25 mu g/ml, 62.5 mu g/ml, 125 mu g/ml, 250 mu g/ml and 500 mu g/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 mu g/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.

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  • 84.
    Nyström, Lina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Al-Rammahi, Noor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Malekkhaiat Häffner, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Browning, Kathryn L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Avidin-biotin cross-linked microgel multilayers as carriers for antimicrobial peptides2018Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, nr 12, s. 4691-4702Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Herein, we report on the formation of cross-linked antimicrobial peptide-loaded microgel multilayers. Poly(ethyl acrylate- co-methacrylic acid) microgels were synthesized and functionalized with biotin to enable the formation of microgel multilayers cross-linked with avidin. Microgel functionalization and avidin cross-linking were verified with infrared spectroscopy, dynamic light scattering, and z-potential measurements, while multilayer formation (up to four layers) was studied with null ellipsometry and quartz crystal microbalance with dissipation (QCM-D). Incorporation of the antimicrobial peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) into the microgel multilayers was achieved either in one shot after multilayer formation or through addition after each microgel layer deposition. The latter was found to strongly promote peptide incorporation. Further, antimicrobial properties of the peptide-loaded microgel multilayers against Escherichia coli were investigated and compared to those of a peptide-loaded microgel monolayer. Results showed a more pronounced suppression in bacterial viability in suspension for the microgel multilayers. Correspondingly, LIVE/DEAD staining showed promoted disruption of adhered bacteria for the KYE28-loaded multilayers. Taken together, cross-linked microgel multilayers thus show promise as high load surface coatings for antimicrobial peptides.

  • 85.
    Nyström, Lina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Nordström, Randi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Saunders, Brian
    Univ Manchester, Manchester, Lancs, England.
    Alvarez-Asencio, Ruben
    KTH, Div Surface Corros Chem, Stockholm, Sweden.
    Rutland, Mark
    KTH, Div Surface Corros Chem, Stockholm, Sweden.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Peptide-loaded microgels as antimicrobial surface coatings2018Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Artikel i tidskrift (Övrigt vetenskapligt)
  • 86.
    Nyström, Lina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Schmidtchen, Artur
    Lund University, Lund, Sweden; University of Copenhagen, Copenhagen, Denmark.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. University of Copenhagen, Copenhagen, Denmark.
    Peptide-Loaded Microgels as Antimicrobial and Anti-Inflammatory Surface Coatings2018Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, nr 8, s. 3456-3466Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we report on covalently immobilized poly(ethyl acrylate- co-methacrylic acid) microgels loaded with the host defense peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), which is derived from human heparin cofactor II, as well as its poly(ethylene glycol)-conjugated (PEGylated) version, KYE28PEG. Peptide loading and release, as well as the consequences of these processes on the microgel and peptide properties, were studied by in situ ellipsometry, confocal microscopy, zeta potential measurements, and circular dichroism spectroscopy. The results show that the microgel-peptide interactions are electrostatically dominated, thus promoted at higher microgel charge density, while PEGylation suppresses peptide binding. PEGylation also enhances the α-helix induction observed for KYE28 upon microgel incorporation. Additionally, peptide release is facilitated at physiological salt concentration, particularly so for KYE28PEG, which illustrates the importance of electrostatic interactions. In vitro studies on Escherichia coli show that the microgel-modified surfaces display potent antifouling properties in both the absence and presence of the incorporated peptide. While contact killing dominates at low ionic strength for the peptide-loaded microgels, released peptides also provide antimicrobial activity in bulk at a high ionic strength. Additionally, KYE28- and KYE28PEG-loaded microgels display anti-inflammatory effects on human monocytes. Taken together, these results not only show that surface-bound microgels offer an interesting approach for local drug delivery of host defense peptides but also illustrate the need to achieve high surface loads of peptides for efficient biological effects.

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  • 87.
    Patel, Seema
    et al.
    San Diego State Univ, Bioinformat & Med Informat Res Ctr, 5500 Campanile Dr, San Diego, CA 92182 USA.
    Homaei, Ahmad
    Univ Hormozgan, Fac Marine Sci & Technol, Dept Marine Biol, Bandar Abbas, Iran;Univ Hormozgan, Dept Biol, Fac Sci, Bandar Abbas, Iran.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. KTH, Sch Chem Sci & Engn, Dept Chem, Ecol Chem Grp, Stockholm, Sweden.
    Akhtar, Nadeem
    Univ Guelph, Dept Anim Biosci, Guelph, ON N1G 2W1, Canada.
    Cathepsins: Proteases that are vital for survival but can also be fatal2018Ingår i: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 105, s. 526-532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The state of enzymes in the human body determines the normal physiology or pathology, so all the six classes of enzymes are crucial. Proteases, the hydrolases, can be of several types based on the nucleophilic amino acid or the metal cofactor needed for their activity. Cathepsins are proteases with serine, cysteine, or aspartic acid residues as the nucleophiles, which are vital for digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, among a litany of other functions. But inflammatory state radically affects their normal roles. Released from the lysosomes, they degrade extracellular matrix proteins such as collagen and elastin, mediating parasite infection, autoimmune diseases, tumor metastasis, cardiovascular issues, and neural degeneration, among other health hazards. Over the years, the different types and isoforms of cathepsin, their optimal pH and functions have been studied, yet much information is still elusive. By taming and harnessing cathepsins, by inhibitors and judicious lifestyle, a gamut of malignancies can be resolved. This review discusses these aspects, which can be of clinical relevance.

  • 88.
    Pubill-Ulldemolins, Cristina
    et al.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland;Univ Sussex, Sch Life Sci, Dept Chem, Brighton BN1 9QJ, E Sussex, England.
    Sharma, Sunil V.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Cartmell, Christopher
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Zhao, Jinlian
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Goss, Rebecca J. M.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Heck Diversification of Indole-Based Substrates under Aqueous Conditions: From Indoles to Unprotected Halo-tryptophans and Halo-tryptophans in Natural Product Derivatives2019Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 25, nr 46, s. 10866-10875Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The blending of synthetic chemistry with biosynthetic processes provides a powerful approach to synthesis. Biosynthetic halogenation and synthetic cross-coupling have great potential to be used together, for small molecule generation, access to natural product analogues and as a tool for chemical biology. However, to enable enhanced generality of this approach, further synthetic tools are needed. Though considerable research has been invested in the diversification of phenylalanine and tyrosine, functionalisation of tryptophans thorough cross-coupling has been largely neglected. Tryptophan is a key residue in many biologically active natural products and peptides; in proteins it is key to fluorescence and dominates protein folding. To this end, we have explored the Heck cross-coupling of halo-indoles and halo-tryptophans in water, showing broad reaction scope. We have demonstrated the ability to use this methodology in the functionalisation of a brominated antibiotic (bromo-pacidamycin), as well as a marine sponge metabolite, barettin.

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  • 89.
    Rasheed, Dalia M.
    et al.
    October 6 Univ, Fac Pharm, Pharmacognosy Dept, Cairo, Egypt..
    Porzel, Andrea
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle An Der Saale, Germany..
    Frolov, Andrei
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle An Der Saale, Germany..
    El Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt..
    Wessjohann, Ludger A.
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle An Der Saale, Germany..
    Farag, Mohamed A.
    Cairo Univ, Coll Pharm, Pharmacognosy Dept, Cairo 11562, Egypt.;Amer Univ Cairo, Sch Sci & Engn, Dept Chem, New Cairo 11835, Egypt..
    Comparative analysis of Hibiscus sabdariffa (roselle) hot and cold extracts in respect to their potential for alpha-glucosidase inhibition2018Ingår i: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 250, s. 236-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative H-1 NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit alpha-glucosidase enzyme.

  • 90.
    Renault, Yohann J. G.
    et al.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Lynch, Rosemary
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Marelli, Enrico
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Sharma, Sunil, V
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Pubill-Ulldemolins, Cristina
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland;Univ Sussex, Dept Chem, Sch Life Sci, Brighton BN1 9QJ, E Sussex, England.
    Sharp, Joshua A.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Cartmell, Christopher
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Goss, Rebecca J. M.
    Univ St Andrews, Dept Chem, St Andrews KY16 9ST, Fife, Scotland;Univ St Andrews, BSRC, St Andrews KY16 9ST, Fife, Scotland.
    Buchwald Hartwig diversification of unprotected halotryptophans, halotryptophan containing tripeptides and the natural product barettin in aqueous conditions2019Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 55, nr 91, s. 13653-13656Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blending synthetic biology and synthetic chemistry represents a powerful approach to diversity complex molecules. To further enable this, compatible synthetic tools are needed. We report the first Buchwald Hartwig amination reactions with unprotected halo-tryptophans under aqueous conditions and demonstrate this methodology is applicable also to the modification of unprotected tripeptides and the natural product barettin.

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  • 91.
    Rubin-Blum, Maxim
    et al.
    Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany;Israel Limnol & Oceanog Res, Tel Shikmona, IL-3108000 Haifa, Israel.
    Antony, Chakkiath Paul
    Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany.
    Sayavedra, Lizbeth
    Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany;Quadram Inst Biosci, Norwich Res Pk, Norwich, Norfolk, England.
    Martinez-Perez, Clara
    Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany.
    Birgel, Daniel
    Univ Hamburg, Ctr Earth Syst Res & Sustainabil, Inst Geol, D-20146 Hamburg, Germany.
    Peckmann, Jörn
    Univ Hamburg, Ctr Earth Syst Res & Sustainabil, Inst Geol, D-20146 Hamburg, Germany.
    Wu, Yu-Chen
    Univ Kiel, RD3 Marine Microbiol & Christian Albrechts, GEOMAR Helmholtz Ctr Ocean Res, Dustembrooker Weg 20, D-24105 Kiel, Germany.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    MacDonald, Ian
    Florida State Univ, POB 3064326, Tallahassee, FL 32306 USA.
    Marcon, Yann
    Helmholtz Ctr Polar & Marine Res, Wegener Inst, HGF MPG Grp Deep Sea Ecol & Technol, Handelshafen 12, D-27570 Bremerhaven, Germany.
    Sahling, Heiko
    Univ Bremen, Ctr Marine Environm Sci, MARUM, D-28359 Bremen, Germany.
    Hentschel, Ute
    Univ Kiel, RD3 Marine Microbiol & Christian Albrechts, GEOMAR Helmholtz Ctr Ocean Res, Dustembrooker Weg 20, D-24105 Kiel, Germany.
    Dubilier, Nicole
    Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany;Univ Bremen, Ctr Marine Environm Sci, MARUM, D-28359 Bremen, Germany.
    Fueled by methane: deep-sea sponges from asphalt seeps gain their nutrition from methane-oxidizing symbionts2019Ingår i: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 13, nr 5, s. 1209-1225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sponges host a remarkable diversity of microbial symbionts, however, the benefit their microbes provide is rarely understood. Here, we describe two new sponge species from deep-sea asphalt seeps and show that they live in a nutritional symbiosis with methane-oxidizing (MOX) bacteria. Metagenomics and imaging analyses revealed unusually high amounts of MOX symbionts in hosts from a group previously assumed to have low microbial abundances. These symbionts belonged to the Marine Methylotrophic Group 2 Glade. They are host-specific and likely vertically transmitted, based on their presence in sponge embryos and streamlined genomes, which lacked genes typical of related free-living MOX. Moreover, genes known to play a role in host-symbiont interactions, such as those that encode eukaryote-like proteins, were abundant and expressed. Methane assimilation by the symbionts was one of the most highly expressed metabolic pathways in the sponges. Molecular and stable carbon isotope patterns of lipids confirmed that methane-derived carbon was incorporated into the hosts. Our results revealed that two species of sponges, although distantly related, independently established highly specific, nutritional symbioses with two closely related methanotrophs. This convergence in symbiont acquisition underscores the strong selective advantage for these sponges in harboring MOX bacteria in the food-limited deep sea.

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  • 92.
    Saeed, A.
    et al.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Larik, F. A.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Jabeen, F.
    Laurentian Univ, Cardiovasc & Metab Res Unit, 935 Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada.
    Mehfooz, H.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Ghumro, S. A.
    Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Ali, M.
    Quaid I Azam Univ, Dept Biol Sci, Islamabad 45320, Pakistan.
    Channar, P. A.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Ashraf, H.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Synthesis, Antibacterial and Antileishmanial Activity, Cytotoxicity, and Molecular Docking of New Heteroleptic Copper(I) Complexes with Thiourea Ligands and Triphenylphosphine2018Ingår i: Russian journal of general chemistry, ISSN 1070-3632, E-ISSN 1608-3350, Vol. 88, nr 3, s. 541-550Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of copper(I) complexes with triphenylphosphine and N-acyl-N'-arylthioureas were synthesized and characterized by elemental analysis and IR and NMR (H-1, C-13, P-31) spectroscopy. The thiourea ligands and their copper(I) triphenylphosphine complexes were screened for antibacterial and antileishmanial activities and cytotoxicity. The synthesized compounds showed much better activity as compared to glucantime and Kanamycin used as reference drugs. The thiourea ligands showed better activity than their Cu(I) complexes. The molecular docking technique was utilized to ascertain the mechanism of action toward molecular targets (GP63 and 16S-rRNA A-site). It was found that the ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces, consistent with the corresponding experimental results. The in silico study of the binding pattern predicted that one of the synthesized ligands, N-(5-chloro-2-nitrophenyl)-N'-pentanoylthiourea, can serve as a potential surrogate for hit-to-lead generation and design of novel antibacterial and antileishmanial agents.

  • 93.
    Saeed, Aamer
    et al.
    Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan.
    Faisal, Muhammad
    Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan.
    Larik, Fayaz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Channar, Pervaiz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad , Pakistan.
    Shahzad, Danish
    Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan.
    Recent Progress in Pyridine Containing Heterocycles as High Performance Host Materials for Blue PHOLEDs2018Ingår i: Mini-Reviews in Organic Chemistry, ISSN 1570-193X, E-ISSN 1875-6298, Vol. 15, nr 4, s. 261-273Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Phosphorescent Organic Light-Emitting Diodes (PHOLEDs) have an advantage of stability for a lifetime in comparison with the conventional Organic Light-Emitting Diodes (OLEDs). Green and red OLEDs have already achieved success, but for the last decade, blue OLEDs have observed a surge in the attention towards them from academia as well as the industry. There are incessant efforts devoted towards the improvement of external quantum efficiency from 25-30%. The host materials (or host compounds), hole transporting and electron transporting are the preeminent factors for the enhancement of External Quantum Efficiency (EQE). This review aims at highlighting the role of pyridine as an efficient Electron Transporting Material (ETM) for blue PHOLEDs. Pyridine having electron withdrawing nature can serve as valuable host compounds for electron transport material in PHOLEDs of a blue color. The presence of nitrogen atom in pyridine facilitates in lowering HOMO/LUMO energy levels compared to benzene ring and this assists in adding phenyl rings at the periphery of pyridine ring.

  • 94.
    Saeed, Aamer
    et al.
    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..
    Larik, Fayaz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Channar, Pervaiz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel2017Ingår i: Chirality, ISSN 0899-0042, E-ISSN 1520-636X, Vol. 29, nr 11, s. 684-707Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments. Worldwide sales of Plavix amounted to $6.4 billion yearly, which ranks second. Attributed to the increased demand of (S)-clopidogrel drug, it provoked the synthetic community to devise facile synthetic approaches. This review aims to summarize the synthetic methods of (S)-clopidogrel drug reported in the literature. The present review discusses the pros and cons of each synthetic methodology, which would be beneficial to the scientific community for further developments in the synthetic methodologies for (S)-clopidogrel. In addition, the compilation approach of literature-reported synthetic strategies of (S)-clopidogrel in one platform is advantageous, supportive, and crucial for the synthetic community to elect the best synthetic methodology of (S)-clopidogrel and to create new synthesis ideas.

  • 95.
    Saleh, Ibrahim A.
    et al.
    Natl Res Ctr, Chem Med Plants Dept, 33 El Bohouth St, Giza 12622, Egypt.
    El Gendy, Abdel Nasser G.
    Natl Res Ctr, Chem Med Plants Dept, 33 El Bohouth St, Giza 12622, Egypt;Natl Res Ctr, Med & Aromat Plants Res Dept, 33 El Bohouth St, Giza 12622, Egypt.
    Afifi, Mohammed A.
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Egypt.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Egypt;Al Rayan Coll, Al Rayan Res & Innovat Ctr, Medina 42541, Saudi Arabia;Jiangsu Univ, Coll Food & Biol Engn, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.
    Microwave Extraction of Essential Oils from Senecio serpens GD Rowly and Comparison with Conventional Hydro-Distillation Method2019Ingår i: Journal of Essential Oil-Bearing Plants (JEOBP), ISSN 0972-060X, E-ISSN 0976-5026, Vol. 22, nr 4, s. 955-961Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Senecio serpens (family Asteraceae) is used as a medicinal plant in Portugal. The present study addressed the chemical profile of essential oils of S. serpens using microwave-assisted extraction (MAE) as a more efficient method for extraction compared to conventional hydro-distillation (HD) method. Gas chromatography-mass spectrometry (GC-MS) analysis of the essential oils identified a total of forty-seven components. According to the results, significant differences were observed in the constituents and percentages of the examined essential oils. Monoterpene hydrocarbons amounted for the major volatile constituents of the extracted oils, where it exhibited a content of 72.09% with MAE and 67.1% with HD. This is the first report of EO composition of the aerials parts of S. serpens. Microwave-assisted extraction presented several advantages as a green method for extraction with higher yield and reduced extraction time.

  • 96.
    Sayed, Abdelwahed R.
    et al.
    KFU, Fac Sci, Dept Chem, Al Hufuf, Saudi Arabia.;Beni Suef Univ, Fac Sci, Dept Chem, Bani Suwayf, Egypt..
    Gomha, Sobhi M.
    Cairo Univ, Fac Sci, Dept Chem, Giza 12613, Egypt.;Islamic Univ Almadinah Almonawara, Fac Sci, Dept Chem, Almadinah Almonawara 42351, Saudi Arabia..
    Taher, Eman A.
    NODCAR, Dept Pharmaceut Chem, Giza 12311, Egypt.;Menoufia Univ, Fac Sci, Chem Dept, Shibin Al Kawm 32512, Egypt..
    Muhammad, Zeinab A.
    NODCAR, Dept Pharmaceut Chem, Giza 12311, Egypt..
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Chem Dept, Shibin Al Kawm 32512, Egypt.
    Gaber, Hatem M.
    NODCAR, Dept Pharmaceut Chem, Giza 12311, Egypt..
    Ahmed, Mahgoub M.
    NODCAR, Mol Drug Evaluat Dept, Giza 12311, Egypt..
    One-Pot Synthesis of Novel Thiazoles as Potential Anti-Cancer Agents2020Ingår i: Drug Design, Development and Therapy, ISSN 1177-8881, E-ISSN 1177-8881, Vol. 14, s. 1363-1375Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Thiazole and thiosemicarbazone derivatives are known to have potential anticancer activity with a mechanism of action related to inhibition of matrix metallo-proteinases, kinases and anti-apoptotic BCL2 family proteins.

    Materials and Methods: A novel three series of 5-(1-(2-(thiazol-2-yl)hydrazono)ethyl) thiazole derivatives were prepared in a one-pot three-component reaction using 2-(2-benzylidene hydrazinyl)-4-methylthiazole as a starting precursor. MS, IR, H-1-NMR and C-13-NMR were used to elucidate the structures of the synthesized compounds. Most of the synthesized products were evaluated for their in vitro anticancer screening against HCT-116, HT-29 and HepG2 using the MTT colorimetric assay.

    Results: The results indicated that compounds 4c, 4d and 8c showed growth inhibition activity against HCT-116 with IC50 values of 3.80 +/- 0.80, 3.65 +/- 0.90 and 3.16 +/- 0.90 mu M, respectively, compared to harmine (IC50 = 2.40 +/- 0.12 mu M) and cisplatin (IC50 = 5.18 +/- 0.94 mu M) reference drugs. Also, compounds 8c, 4d and 4c showed promising IC(50 )values of 3.47 +/- 0.79, 4.13 +/- 0.51 and 7.24 +/- 0.62 mu M, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC50 = 4.59 +/- 0.67 mu M) and cisplatin (IC50 = 11.68 +/- 1.54 mu M). On the other hand, compounds 4d, 4c, 8c and llc were the most active (IC50 values of 2.31 +/- 0.43, 2.94 +/- 0.62, 4.57 +/- 0.85 and 9.86 +/- 0.78 mu M, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC50 = 2.54 +/- 0.82 mu M) and cisplatin (IC50 = 41 +/- 0.63 pM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds (4c, 4d and 8c) inside HCT-116 cells was apoptosis through the Bcl-2 family.

    Conclusion: Thiazole scaffolds 4c, 4d and 8c showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.

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  • 97.
    Shahid, Shereena
    et al.
    Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    Faisal, Muhammad
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Ghumro, Sarfaraz Ali
    Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Rasheed, Samina
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Abbas, Nadir
    Univ Hail, Dept Chem Engn, Hail, Saudi Arabia.
    Larik, Fayaz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Channar, Pervaiz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Fattah, Tanzeela Abdul
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Ashraf, Zaman
    Allama Iqbal Open Univ, Dept Chem, Islamabad 44000, Pakistan.
    Solangi, Zulfiqar Ali
    Shah Abdul Latif Univ, Dept Chem, Khairpur, Pakistan.
    A Review on the Scope of TFDO-Mediated Oxidation in Organic Synthesis-Reactivity and Selectivity2018Ingår i: Current Organic Synthesis, ISSN 1570-1794, E-ISSN 1875-6271, Vol. 15, nr 8, s. 1091-1108Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Dioxiranes are three-membered strained ring peroxides that are typical archetype examples of electrophilic entities. A dioxirane-based oxidant named 3-methyl(trifluoromethyl)dioxirane (TFDO) is a fluorinated analogue of the extremely valuable oxidant dimethyldioxirane (DMDO). Owing to the strained three-membered ring and presence of electron-withdrawing trifluoromethyl group, TFDO is several times more reactive than DMDO and acts as a significant chemical reagent. Moreover, TFDO exhibits high regio-, chemo- and stereo-selectivity even under unusual reaction conditions, i.e. at pH values close to neutrality and at sub-ambient temperatures. The TFDO transfers an oxygen atom to "unactivated" carbon-hydrogen bonds of alkanes as well as to the double bonds of alkenes and also helps in oxidation of compounds containing heteroatoms having a lone pair of electrons, such as sulfides and amines. TFDO-mediated oxidation is considered to be one of the main procedures in the 21st century for the synthesis of oxygen-containing organic molecules. This review throws light on the applications of TFDO in organic syntheses to provide an insight into the future research and gives a comprehensive summary of the selective functionalization of activated and non-activated organic compounds.

  • 98.
    Shahzad, Danish
    et al.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Larik, Fayaz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Channar, Pervaiz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Abbas, Qamar
    Univ Sindh, Dept Physiol, Jamshoro 76080, Pakistan.
    Alajmi, Mohamed F.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    Arshad, M. Ifzan
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Erben, Mauricio F.
    UNLP, CONICET, CEQUINOR, Dept Quim,Fac Ciencias Exactas,CCT La Plata, Blvd 120 E-60 & 64 1465, RA-1900 La Plata, Argentina.
    Hassan, Mubashir
    Kongju Natl Univ, Coll Nat Sci, Dept Biol Sci, 56 Gongjudehak Ro, Gongju 32588, Chungnam, South Korea.
    Raza, Hussain
    Kongju Natl Univ, Coll Nat Sci, Dept Biol Sci, 56 Gongjudehak Ro, Gongju 32588, Chungnam, South Korea.
    Seo, Sung-Yum
    Kongju Natl Univ, Coll Nat Sci, Dept Biol Sci, 56 Gongjudehak Ro, Gongju 32588, Chungnam, South Korea.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Novel C-2 Symmetric Molecules as -Glucosidase and -Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics2019Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 8, artikel-id 1511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by H-1-NMR and C-13-NMR, and evaluated for their in vitro -glucosidase and -amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both -glucosidase and -amylase. The IC50 of 5g against -glucosidase was 0.35917 +/- 0.0189 mu M (standard acarbose IC50 = 6.109 +/- 0.329 mu M), and the IC50 value of 5g against -amylase was 0.4379 +/- 0.0423 mu M (standard acarbose IC50 = 33.178 +/- 2.392 mu M). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of -glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 angstrom, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results

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  • 99.
    Shcherbakova, A.
    et al.
    Friedrich Wilhelms Univ Bonn, Med Clin 3, UKB, Sigmund Freudstr 25, D-53127 Bonn, Germany.;Dept Forestry, Ploshchad Lenina 3, Yoshkar Ola 424000, Mari El Republi, Russia..
    Nyugen, L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Friedrich Wilhelms Univ Bonn, Med Clin 3, UKB, Sigmund Freudstr 25, D-53127 Bonn, Germany..
    Koptina, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Shurgin, A.
    Dept Forestry, Ploshchad Lenina 3, Yoshkar Ola 424000, Mari El Republi, Russia..
    Romanov, E.
    Dept Forestry, Ploshchad Lenina 3, Yoshkar Ola 424000, Mari El Republi, Russia..
    Ulrich-Merzenich, G.
    Friedrich Wilhelms Univ Bonn, Med Clin 3, UKB, Sigmund Freudstr 25, D-53127 Bonn, Germany..
    Screening of compounds of Evernia prunastri (L.) for their antiproliferative activity in glioblastoma cells2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Artikel i tidskrift (Övrigt vetenskapligt)
  • 100.
    Slazak, Blazej
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Polish Acad Sci, W Szafer Inst Bot, Krakow, Poland.
    Kapusta, Malgorzata
    Univ Gdansk, Fac Biol, Dept Plant Cytol & Embryol, Gdansk, Poland.
    Strömstedt, Adam A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Slomka, Aneta
    Jagiellonian Univ, Inst Bot, Dept Plant Cytol & Embryol, Gdansk, Poland.
    Krychowiak, Marta
    Univ Gdansk, Intercollegiate Fac Biotechnol, Lab Biol Act Cpds, Gdansk, Poland;Med Univ Gdansk, Gdansk, Poland.
    Shariatgorji, Mohammadreza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Andrén, Per E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bohdanowicz, Jerzy
    Univ Gdansk, Fac Biol, Dept Plant Cytol & Embryol, Gdansk, Poland.
    Kuta, Elzbieta
    Jagiellonian Univ, Inst Bot, Dept Plant Cytol & Embryol, Gdansk, Poland.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    How Does the Sweet Violet (Viola odorata L.) Fight Pathogens and Pests - Cyclotides as a Comprehensive Plant Host Defense System2018Ingår i: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 9, artikel-id 1296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are cyclic plant polypeptides of 27-37 amino acid residues. They have been extensively studied in bioengineering and drug development contexts. However, less is known about the relevance of cyclotides for the plants producing them. The anti-insect larvae effects of kB1 and antibacterial activity of cyO2 suggest that cyclotides are a part of plant host defense. The sweet violet (Viola odorata L.) produces a wide array of cyclotides, including kB1 (kalata B1) and cyO2 (cycloviolacin O2), with distinct presumed biological roles. Here, we evaluate V. odorata cyclotides' potency against plant pathogens and their mode of action using bioassays, liposome experiments and immunogold labeling for transmission electron microscopy (TEM). We explore the link between the biological activity and distribution in plant generative, vegetative tissues and seeds, depicted by immunohistochemistry and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Cyclotides cyO2, cyO3, cyO13, and cyO19 are shown to have potent activity against model fungal plant pathogens (Fusarium oxysporum, F. graminearum, F. culmorum, Mycosphaerella fragariae, Botrytis cinerea) and fungi isolated from violets (Colletotrichum utrechtense and Alternaria alternata), with minimal inhibitory concentrations (MICs) ranging from 0.8 to 25 mu M. Inhibition of phytopathogenic bacteria - Pseudomonas syringae pv. syringae, Dickeya dadantii and Pectobacterium atrosepticum - is also observed with MIC = 25-100 mu M. A membrane-disrupting antifungal mode of action is shown. Finding cyO2 inside the fungal spore cells in TEM images may indicate that other, intracellular targets may be involved in the mechanism of toxicity. Fungi can not break down cyclotides in the course of days. varv A (kalata S) and kB1 show little potency against pathogenic fungi when compared with the tested cycloviolacins. cyO2, cyO3, cyO19 and kB1 are differentially distributed and found in tissues vulnerable to pathogen (epidermis, rizodermis, vascular bundles, protodermis, procambium, ovary walls, outer integuments) and pest ( ground tissues of leaf and petiole) attacks, respectively, indicating a link between the cyclotides' sites of accumulation and biological role. Cyclotides emerge as a comprehensive defense system in V. odorata, in which different types of peptides have specific targets that determine their distribution in plant tissues.

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