Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms

The papers of this thesis are not available in Munin: I. K. Ø. Hanssen, J. H. Andersen, T. Stiberg, R. A. Engh, J. Svenson, A.-M Genevière, E. Hansen.: 'Antitumoral and Mechanistic Studies of Ianthelline Isolated from the Arctic Sponge Stryphnus fortis'. Anticancer research, 2012, 32, 4287...

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Main Author: Hanssen, Kine Østnes
Format: Doctoral or Postdoctoral Thesis
Language:English
Published: UiT The Arctic University of Norway 2014
Subjects:
Online Access:https://hdl.handle.net/10037/7017
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institution Open Polar
collection University of Tromsø: Munin Open Research Archive
op_collection_id ftunivtroemsoe
language English
topic Marine bioprospecting
DOKTOR-002
spellingShingle Marine bioprospecting
DOKTOR-002
Hanssen, Kine Østnes
Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
topic_facet Marine bioprospecting
DOKTOR-002
description The papers of this thesis are not available in Munin: I. K. Ø. Hanssen, J. H. Andersen, T. Stiberg, R. A. Engh, J. Svenson, A.-M Genevière, E. Hansen.: 'Antitumoral and Mechanistic Studies of Ianthelline Isolated from the Arctic Sponge Stryphnus fortis'. Anticancer research, 2012, 32, 4287 – 4297. Available at http://ar.iiarjournals.org/content/32/10/4287.abstract?sid=976499ec-bb0d-47f5-962c-fde535c84393 II. K. Ø. Hanssen, G. Cervin, R. Trepos, J. Petitbois, T. Haug, E. Hansen, J. H. Andersen, H. Pavia, C. Hellio, J. Svenson.: ‘The Bromotyrosine Derivative Ianthelline Isolated from the Arctic Marine Sponge Stryphnus fortis Inhibits Marine Micro- and Macrobiofouling’. Marine Biotechnology, 2014, Volume 16, Issue 6, pp 684-694. Available at http://dx.doi.org/10.1007/s10126-014-9583-y III:K. Ø. Hanssen, B. Schuler, A. J. Williams, T. B. Demissie, E. Hansen, J. H. Andersen, J. Svenson, K. Blinov, M. Repisky, F. Mohn, G. Meyer, J.-S. Svendsen, K. Ruud, M. Elyashberg, L. Gross, M. Jaspars, J. Isaksson.: ‘A combined Atomic Force Microscopy and Computational Approach for the Structural Elucidation of Breitfussin A and B: Highly Modified Halogenated Dipeptides from Thuiaria Breitfussi’. Angewandte Chemie International Edition, 2012, 51, 12238-12241. Available at http://dx.doi.org/10.1002/anie.201203960 The list of achievements in developing pharmaceuticals and other useful products originating from Nature is long, and it continues to extend. Marine bioprospecting alone has generated three novel drugs in the last four years. The continued success motivates further bioprospecting efforts in the search for utilisable products from natural sources. In this thesis, extracts of Arctic marine organisms were screened for bioactivity. Bioactive extracts were dereplicated using high-resolution mass spectrometry (HR-MS) in an attempt to identify the component(s) responsible for the observed bioactivity and later isolate them using mass guided fractionation. This approach led to the isolation of ianthelline, a previously reported bromotyrosine-derived compound from the sponge Stryphnus fortis as well as two novel, highly modified dipeptides, breitfussin A and B, from the hydrozoa Thuiaria breitfussi. Even though the structure of ianthelline was reported in 1986 by Litaudon et al. very limited bioactivity data was available. The potential of ianthelline as an anticancer agent was explored in paper I. Ianthelline inhibited cellular growth in a dose- and time dependent manner by several mechanisms, including inhibition of mitotic spindle formation and inhibition of protein kinase activity. In paper II, ianthelline was investigated for antibiofouling activity. The compound was found to inhibit all the major stages of the biofouling process, with the main effect being inhibition of marine bacterial growth and the settlement of barnacles. By dereplication, breitfussin A and B were suspected to be novel compounds, with proton poor molecular compositions of C16H11N3O2BrI and C16H11N3O2Br2, respectively. The high ratio of heavy atoms to protons, in addition to low isolation yields, complicated the structure elucidation of the two compounds. In the end, their structures could be elucidated using a combination of HR-MS analysis, nuclear magnetic resonance (NMR) spectroscopy, computer-assisted structure elucidation (CASE)- and density functional theory (DFT) calculations as well as atomic force microscopy (AFM) imaging. This represents the first example of AFM as a tool used for structure elucidation of a novel, natural product.
format Doctoral or Postdoctoral Thesis
author Hanssen, Kine Østnes
author_facet Hanssen, Kine Østnes
author_sort Hanssen, Kine Østnes
title Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
title_short Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
title_full Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
title_fullStr Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
title_full_unstemmed Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms
title_sort isolation and characterisation of bioactive secondary metabolites from arctic, marine organisms
publisher UiT The Arctic University of Norway
publishDate 2014
url https://hdl.handle.net/10037/7017
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ENVELOPE(14.033,14.033,65.379,65.379)
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geographic Arctic
Cervin
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Haug
Ruud
Stiberg
geographic_facet Arctic
Cervin
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Haug
Ruud
Stiberg
genre Arctic
genre_facet Arctic
op_relation 978-82-8266-090-7
https://hdl.handle.net/10037/7017
URN:NBN:no-uit_munin_6605
op_rights openAccess
Copyright 2014 The Author(s)
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spelling ftunivtroemsoe:oai:munin.uit.no:10037/7017 2023-05-15T14:59:27+02:00 Isolation and Characterisation of Bioactive Secondary Metabolites from Arctic, Marine Organisms Hanssen, Kine Østnes 2014-12-09 https://hdl.handle.net/10037/7017 eng eng UiT The Arctic University of Norway UiT Norges arktiske universitet 978-82-8266-090-7 https://hdl.handle.net/10037/7017 URN:NBN:no-uit_munin_6605 openAccess Copyright 2014 The Author(s) Marine bioprospecting DOKTOR-002 Doctoral thesis Doktorgradsavhandling 2014 ftunivtroemsoe 2021-06-25T17:54:04Z The papers of this thesis are not available in Munin: I. K. Ø. Hanssen, J. H. Andersen, T. Stiberg, R. A. Engh, J. Svenson, A.-M Genevière, E. Hansen.: 'Antitumoral and Mechanistic Studies of Ianthelline Isolated from the Arctic Sponge Stryphnus fortis'. Anticancer research, 2012, 32, 4287 – 4297. Available at http://ar.iiarjournals.org/content/32/10/4287.abstract?sid=976499ec-bb0d-47f5-962c-fde535c84393 II. K. Ø. Hanssen, G. Cervin, R. Trepos, J. Petitbois, T. Haug, E. Hansen, J. H. Andersen, H. Pavia, C. Hellio, J. Svenson.: ‘The Bromotyrosine Derivative Ianthelline Isolated from the Arctic Marine Sponge Stryphnus fortis Inhibits Marine Micro- and Macrobiofouling’. Marine Biotechnology, 2014, Volume 16, Issue 6, pp 684-694. Available at http://dx.doi.org/10.1007/s10126-014-9583-y III:K. Ø. Hanssen, B. Schuler, A. J. Williams, T. B. Demissie, E. Hansen, J. H. Andersen, J. Svenson, K. Blinov, M. Repisky, F. Mohn, G. Meyer, J.-S. Svendsen, K. Ruud, M. Elyashberg, L. Gross, M. Jaspars, J. Isaksson.: ‘A combined Atomic Force Microscopy and Computational Approach for the Structural Elucidation of Breitfussin A and B: Highly Modified Halogenated Dipeptides from Thuiaria Breitfussi’. Angewandte Chemie International Edition, 2012, 51, 12238-12241. Available at http://dx.doi.org/10.1002/anie.201203960 The list of achievements in developing pharmaceuticals and other useful products originating from Nature is long, and it continues to extend. Marine bioprospecting alone has generated three novel drugs in the last four years. The continued success motivates further bioprospecting efforts in the search for utilisable products from natural sources. In this thesis, extracts of Arctic marine organisms were screened for bioactivity. Bioactive extracts were dereplicated using high-resolution mass spectrometry (HR-MS) in an attempt to identify the component(s) responsible for the observed bioactivity and later isolate them using mass guided fractionation. This approach led to the isolation of ianthelline, a previously reported bromotyrosine-derived compound from the sponge Stryphnus fortis as well as two novel, highly modified dipeptides, breitfussin A and B, from the hydrozoa Thuiaria breitfussi. Even though the structure of ianthelline was reported in 1986 by Litaudon et al. very limited bioactivity data was available. The potential of ianthelline as an anticancer agent was explored in paper I. Ianthelline inhibited cellular growth in a dose- and time dependent manner by several mechanisms, including inhibition of mitotic spindle formation and inhibition of protein kinase activity. In paper II, ianthelline was investigated for antibiofouling activity. The compound was found to inhibit all the major stages of the biofouling process, with the main effect being inhibition of marine bacterial growth and the settlement of barnacles. By dereplication, breitfussin A and B were suspected to be novel compounds, with proton poor molecular compositions of C16H11N3O2BrI and C16H11N3O2Br2, respectively. The high ratio of heavy atoms to protons, in addition to low isolation yields, complicated the structure elucidation of the two compounds. In the end, their structures could be elucidated using a combination of HR-MS analysis, nuclear magnetic resonance (NMR) spectroscopy, computer-assisted structure elucidation (CASE)- and density functional theory (DFT) calculations as well as atomic force microscopy (AFM) imaging. This represents the first example of AFM as a tool used for structure elucidation of a novel, natural product. Doctoral or Postdoctoral Thesis Arctic University of Tromsø: Munin Open Research Archive Arctic Cervin ENVELOPE(140.017,140.017,-66.664,-66.664) Hanssen ENVELOPE(-164.467,-164.467,-85.983,-85.983) Haug ENVELOPE(15.188,15.188,67.918,67.918) Ruud ENVELOPE(14.033,14.033,65.379,65.379) Stiberg ENVELOPE(17.523,17.523,68.207,68.207)