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  1. Artikel ; Online: Sponging off nature for new drug leads.

    Andersen, Raymond J

    Biochemical pharmacology

    2017  Band 139, Seite(n) 3–14

    Abstract: Marine sponges have consistently been the richest source of new marine natural products with unprecedented chemical scaffolds and potent biological activities that have been reported in the chemical literature since the early 1970s. During the last ... ...

    Abstract Marine sponges have consistently been the richest source of new marine natural products with unprecedented chemical scaffolds and potent biological activities that have been reported in the chemical literature since the early 1970s. During the last 40years, chemists in the Andersen laboratory at UBC, in collaboration with biologists, have discovered many novel bioactive sponge natural products. Four experimental drug candidates for treatment of inflammation and cancer, that were inspired by members of this sponge natural product collection, have progressed to phase I/II/III clinical trials. This review recounts the scientific stories behind the discovery and development of these four drug candidates; IPL576,092, HTI-286 (Taltobulin), EPI-506 (Ralaniten acetate), and AQX-1125.
    Mesh-Begriff(e) Animals ; Anti-Asthmatic Agents/adverse effects ; Anti-Asthmatic Agents/chemistry ; Anti-Asthmatic Agents/pharmacology ; Anti-Asthmatic Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antimitotic Agents/adverse effects ; Antimitotic Agents/chemistry ; Antimitotic Agents/pharmacology ; Antimitotic Agents/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Aquatic Organisms/chemistry ; Benzhydryl Compounds/adverse effects ; Benzhydryl Compounds/chemistry ; Benzhydryl Compounds/pharmacology ; Benzhydryl Compounds/therapeutic use ; Biological Products/chemistry ; Biological Products/isolation & purification ; Cyclohexanols/adverse effects ; Cyclohexanols/chemistry ; Cyclohexanols/therapeutic use ; Drug Design ; Drug Discovery ; Drugs, Investigational/adverse effects ; Drugs, Investigational/chemistry ; Drugs, Investigational/pharmacology ; Drugs, Investigational/therapeutic use ; Glycerol/analogs & derivatives ; Glycerol/pharmacology ; Glycerol/therapeutic use ; Humans ; Indans/adverse effects ; Indans/chemistry ; Indans/therapeutic use ; Nonsteroidal Anti-Androgens/adverse effects ; Nonsteroidal Anti-Androgens/chemistry ; Nonsteroidal Anti-Androgens/pharmacology ; Nonsteroidal Anti-Androgens/therapeutic use ; Oligopeptides/adverse effects ; Oligopeptides/chemistry ; Oligopeptides/pharmacology ; Oligopeptides/therapeutic use ; Porifera/chemistry ; Prodrugs/adverse effects ; Prodrugs/chemistry ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; Pyrrolidinones/adverse effects ; Pyrrolidinones/chemistry ; Pyrrolidinones/isolation & purification ; Pyrrolidinones/therapeutic use ; Sterols/adverse effects ; Sterols/chemistry ; Sterols/pharmacology ; Sterols/therapeutic use
    Chemische Substanzen 4-(4-(aminomethyl)-7a-methyl-1-methylideneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexan-1-ol ; Anti-Asthmatic Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Antimitotic Agents ; Antineoplastic Agents ; Benzhydryl Compounds ; Biological Products ; Cyclohexanols ; Drugs, Investigational ; HTI-286 ; IPL576,092 ; Indans ; Nonsteroidal Anti-Androgens ; Oligopeptides ; Prodrugs ; Pyrrolidinones ; Sterols ; Glycerol (PDC6A3C0OX)
    Sprache Englisch
    Erscheinungsdatum 2017-09-01
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2017.04.012
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Biologically active marine natural products and their molecular targets discovered using a chemical genetics approach.

    Williams, David E / Andersen, Raymond J

    Natural product reports

    2019  Band 37, Heft 5, Seite(n) 617–633

    Abstract: Covering: 2000 to 2019The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains ...

    Abstract Covering: 2000 to 2019The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains the vitality of natural products chemistry research. Unfortunately, finding these important new compounds is neither routine or trivial and a major challenge is finding effective discovery paradigms. This review presents examples that illustrate the effectiveness of a chemical genetics approach to marine natural product (MNP) discovery that intertwines compound discovery, molecular target identification, and phenotypic response/biological activity. The examples include MNPs that have complex unprecedented structures, new or understudied molecular targets, and potent biological activities of therapeutic interest. A variety of methods to identify molecular targets are also featured.
    Mesh-Begriff(e) Animals ; Aquatic Organisms ; Biological Products/chemistry ; Biological Products/metabolism ; Biological Products/pharmacology ; Drug Discovery/methods ; Glycoside Hydrolase Inhibitors/chemistry ; Glycoside Hydrolase Inhibitors/pharmacology ; Histone-Lysine N-Methyltransferase/antagonists & inhibitors ; Histone-Lysine N-Methyltransferase/metabolism ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Phenotype ; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/metabolism
    Chemische Substanzen Biological Products ; Glycoside Hydrolase Inhibitors ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; KMT5A protein, human (EC 2.1.1.43) ; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases (EC 3.1.3.86)
    Sprache Englisch
    Erscheinungsdatum 2019-11-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2002546-4
    ISSN 1460-4752 ; 0265-0568
    ISSN (online) 1460-4752
    ISSN 0265-0568
    DOI 10.1039/c9np00054b
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Marine sponge-derived/inspired drugs and their applications in drug delivery systems.

    Ramanjooloo, Avin / Andersen, Raymond J / Bhaw-Luximon, Archana

    Future medicinal chemistry

    2021  Band 13, Heft 5, Seite(n) 487–504

    Abstract: Oceans harbor a vast biodiversity that is not represented in terrestrial habitats. Marine sponges have been the richest source of marine natural products reported to date, and sponge-derived natural products have served as inspiration for the development ...

    Abstract Oceans harbor a vast biodiversity that is not represented in terrestrial habitats. Marine sponges have been the richest source of marine natural products reported to date, and sponge-derived natural products have served as inspiration for the development of several drugs in clinical use. However, many promising sponge-derived drug candidates have been stalled in clinical trials due to lack of efficacy, off-target toxicity, metabolic instability or poor pharmacokinetics. One possible solution to this high clinical failure rate is to design drug delivery systems that deliver drugs in a controlled and specific manner. This review critically analyzes drugs/drug candidates inspired by sponge natural products and the potential use of drug delivery systems as a new strategy to enhance the success rate for translation into clinical use.
    Mesh-Begriff(e) Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; Biological Products/chemistry ; Biological Products/metabolism ; Biological Products/pharmacology ; Biological Products/therapeutic use ; Cell Cycle Checkpoints/drug effects ; Drug Carriers/chemistry ; Herpesviridae/drug effects ; Immunoconjugates/chemistry ; Immunoconjugates/metabolism ; Immunoconjugates/therapeutic use ; Neoplasms/drug therapy ; Porifera/metabolism
    Chemische Substanzen Antineoplastic Agents ; Antiviral Agents ; Biological Products ; Drug Carriers ; Immunoconjugates
    Sprache Englisch
    Erscheinungsdatum 2021-02-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ISSN 1756-8927
    ISSN (online) 1756-8927
    DOI 10.4155/fmc-2020-0123
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Dentigerumycin F and G: Dynamic structures retrieved through a genome-mining/nitrogen-NMR methodology

    Morgan, Kalindi D. / Williams, David E. / Ryan, Katherine S. / Andersen, Raymond J.

    Tetrahedron letters. 2022 Mar. 30, v. 94

    2022  

    Abstract: Continual efforts to unearth new natural product chemistry expands our understanding of the scope of chemical space. Here we report the two low-abundance piperazic acid-containing linear peptides dentigerumycins F (1) and G (2), discovered through a ... ...

    Abstract Continual efforts to unearth new natural product chemistry expands our understanding of the scope of chemical space. Here we report the two low-abundance piperazic acid-containing linear peptides dentigerumycins F (1) and G (2), discovered through a combined genome-mining/¹⁵N NMR-based discovery method. Dentigerumycins F and G demonstrate a dynamic equilibrium in their oxane ring systems, which complicated structure elucidation. The application of various NMR solvents and conditions revealed the constitution of these natural products.
    Schlagwörter chemistry ; methodology ; new products ; peptides ; solvents
    Sprache Englisch
    Erscheinungsverlauf 2022-0330
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    ZDB-ID 204287-3
    ISSN 1873-3581 ; 0040-4039
    ISSN (online) 1873-3581
    ISSN 0040-4039
    DOI 10.1016/j.tetlet.2022.153688
    Datenquelle NAL Katalog (AGRICOLA)

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 2837: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Artikel: Biologically active marine natural products and their molecular targets discovered using a chemical genetics approach

    Williams, David E. / Andersen, Raymond J.

    Natural product reports. 2020 May 27, v. 37, no. 5

    2020  

    Abstract: The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains the vitality of ... ...

    Abstract The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains the vitality of natural products chemistry research. Unfortunately, finding these important new compounds is neither routine or trivial and a major challenge is finding effective discovery paradigms. This review presents examples that illustrate the effectiveness of a chemical genetics approach to marine natural product (MNP) discovery that intertwines compound discovery, molecular target identification, and phenotypic response/biological activity. The examples include MNPs that have complex unprecedented structures, new or understudied molecular targets, and potent biological activities of therapeutic interest. A variety of methods to identify molecular targets are also featured.
    Schlagwörter bioactive properties ; phenotype ; therapeutics
    Sprache Englisch
    Erscheinungsverlauf 2020-0527
    Umfang p. 617-633.
    Erscheinungsort The Royal Society of Chemistry
    Dokumenttyp Artikel
    ZDB-ID 2002546-4
    ISSN 1460-4752 ; 0265-0568
    ISSN (online) 1460-4752
    ISSN 0265-0568
    DOI 10.1039/c9np00054b
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  6. Artikel: Isolation of a natural product with anti-mitotic activity from a toxic Canadian prairie plant.

    Molina, Layla / Williams, David E / Andersen, Raymond J / Golsteyn, Roy M

    Heliyon

    2021  Band 7, Heft 5, Seite(n) e07131

    Abstract: We are investigating plants from the prairie ecological zone of Canada to identify natural products that inhibit mitosis in cancer cells. Investigation of plant parts from the Canadian plant ... ...

    Abstract We are investigating plants from the prairie ecological zone of Canada to identify natural products that inhibit mitosis in cancer cells. Investigation of plant parts from the Canadian plant species
    Sprache Englisch
    Erscheinungsdatum 2021-05-24
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e07131
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: New norclerodane diterpenoids from bulbils of

    Somteds, Apisara / Kanokmedhakul, Somdej / Yahuafai, Jantana / Opanasopit, Praneet / Patrick, Brian O / Andersen, Raymond J / Kanokmedhakul, Kwanjai

    Natural product research

    2023  , Seite(n) 1–8

    Abstract: Investigation of extracts from bulbils ... ...

    Abstract Investigation of extracts from bulbils of
    Sprache Englisch
    Erscheinungsdatum 2023-07-26
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2185747-7
    ISSN 1478-6427 ; 1478-6419
    ISSN (online) 1478-6427
    ISSN 1478-6419
    DOI 10.1080/14786419.2023.2237172
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  8. Artikel ; Online: Alkaloids and Styryl lactones from

    Polbuppha, Isaraporn / Teerapongpisan, Passakorn / Phukhatmuen, Piyaporn / Suthiphasilp, Virayu / Maneerat, Tharakorn / Charoensup, Rawiwan / Andersen, Raymond J / Laphookhieo, Surat

    Molecules (Basel, Switzerland)

    2023  Band 28, Heft 3

    Abstract: Gonioridleylactam ( ...

    Abstract Gonioridleylactam (
    Mesh-Begriff(e) Goniothalamus/chemistry ; alpha-Glucosidases ; Lactones/pharmacology ; Lactones/chemistry ; Alkaloids ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Molecular Structure ; Glycoside Hydrolase Inhibitors/pharmacology ; Glycoside Hydrolase Inhibitors/chemistry
    Chemische Substanzen alpha-Glucosidases (EC 3.2.1.20) ; Lactones ; Alkaloids ; Plant Extracts ; Glycoside Hydrolase Inhibitors
    Sprache Englisch
    Erscheinungsdatum 2023-01-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28031158
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    Zs.MO 81: Hefte anzeigen

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  9. Artikel ; Online: Phaeanthuslucidines A-D, dimeric aporphine alkaloid derivatives from Phaeanthus lucidus Oliv.

    Teerapongpisan, Passakorn / Suthiphasilp, Virayu / Kumboonma, Pakit / Maneerat, Tharakorn / Duangyod, Thidarat / Charoensup, Rawiwan / Andersen, Raymond J / Laphookhieo, Surat

    Phytochemistry

    2023  Band 212, Seite(n) 113717

    Abstract: The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, ... ...

    Abstract The first phytochemical investigation of the twigs of Phaeanthus lucidus Oliv. resulted in the isolation and identification of four undescribed alkaloids, including two aporphine dimers, phaeanthuslucidines A and B, a hybrid of aristolactam-aporphine, phaeanthuslucidine C, and a C-N linked aporphine dimer, phaeanthuslucidine D, together with two known compounds. Their structures were determined by extensive analysis of spectroscopic data, and by comparison of their spectroscopic and physical data with previous reports. Phaeanthuslucidines A-C and bidebiline E were analysed and resolved by chiral HPLC to yield the (R
    Mesh-Begriff(e) Molecular Docking Simulation ; alpha-Glucosidases ; Molecular Structure ; Alkaloids/chemistry ; Aporphines/chemistry ; Annonaceae/chemistry ; Antineoplastic Agents
    Chemische Substanzen alpha-Glucosidases (EC 3.2.1.20) ; Alkaloids ; Aporphines ; Antineoplastic Agents
    Sprache Englisch
    Erscheinungsdatum 2023-05-13
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 208884-8
    ISSN 1873-3700 ; 0031-9422
    ISSN (online) 1873-3700
    ISSN 0031-9422
    DOI 10.1016/j.phytochem.2023.113717
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    Verfügbar in ZB MED Bonn

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  10. Artikel: Isolation of a natural product with anti-mitotic activity from a toxic Canadian prairie plant

    Molina, Layla / Williams, David E / Andersen, Raymond J / Golsteyn, Roy M

    Heliyon. 2021 May, v. 7, no. 5

    2021  

    Abstract: We are investigating plants from the prairie ecological zone of Canada to identify natural products that inhibit mitosis in cancer cells. Investigation of plant parts from the Canadian plant species Hymenoxys richardsonii (Asteraceae) revealed that leaf ... ...

    Abstract We are investigating plants from the prairie ecological zone of Canada to identify natural products that inhibit mitosis in cancer cells. Investigation of plant parts from the Canadian plant species Hymenoxys richardsonii (Asteraceae) revealed that leaf extracts (PP-360A) had anti-mitotic activity on human cancer cell lines. Cells treated with leaf extracts acquired a rounded morphology, similar to that of cells in mitosis. We demonstrated that the rounded cells contained mitotic spindles and phospho-histone H3 using the techniques of immunofluorescence microscopy. By biology-guided fractionation of H. richardsonii leaves, we isolated a sesquiterpene lactone named hymenoratin, which had not been previously assigned a biological activity. Cells treated with hymenoratin have phospho-histone H3 positive chromosomes, a mitotic spindle, and enter a prolonged mitotic arrest in which the spindles become distorted. By Western blot analysis, hymenoratin treated cells acquire high levels of cyclin B and dephosphorylated Cdk1. There is a growing body of evidence that select members of the sesquiterpene lactone chemical family have anti-mitotic activity.
    Schlagwörter Hymenoxys richardsonii ; Western blotting ; cyclins ; fluorescence microscopy ; fractionation ; humans ; leaves ; mitosis ; mitotic spindle apparatus ; neoplasm cells ; sesquiterpenoids ; toxicity ; Canada
    Sprache Englisch
    Erscheinungsverlauf 2021-05
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    Anmerkung NAL-AP-2-clean
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e07131
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