Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines
Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. T...
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ftunivtroemsoe:oai:munin.uit.no:10037/28137 2023-05-15T14:25:43+02:00 Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines Østnes Hansen, Kine Hansen, Ida Kristine Østnes Ullsten-Wahlund, Sara Jenssen, Marte Isaksson, Johan Mattias Li, Chun Schneider, Yannik K.-H. 2022-12-13 https://hdl.handle.net/10037/28137 https://doi.org/10.3390/ijms232415852 eng eng MDPI International Journal of Molecular Sciences Østnes Hansen, Hansen, Ullsten-Wahlund, Jenssen, Petit, Isaksson. Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines. International Journal of Molecular Sciences. 2022 FRIDAID 2103455 doi:10.3390/ijms232415852 1661-6596 1422-0067 https://hdl.handle.net/10037/28137 Attribution 4.0 International (CC BY 4.0) openAccess Copyright 2022 The Author(s) https://creativecommons.org/licenses/by/4.0 CC-BY Journal article Tidsskriftartikkel Peer reviewed publishedVersion 2022 ftunivtroemsoe https://doi.org/10.3390/ijms232415852 2023-01-12T00:02:51Z Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated. Article in Journal/Newspaper Arctic Arctic University of Tromsø: Munin Open Research Archive Arctic International Journal of Molecular Sciences 23 24 15852 |
institution |
Open Polar |
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University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
description |
Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated. |
format |
Article in Journal/Newspaper |
author |
Østnes Hansen, Kine Hansen, Ida Kristine Østnes Ullsten-Wahlund, Sara Jenssen, Marte Isaksson, Johan Mattias Li, Chun Schneider, Yannik K.-H. |
spellingShingle |
Østnes Hansen, Kine Hansen, Ida Kristine Østnes Ullsten-Wahlund, Sara Jenssen, Marte Isaksson, Johan Mattias Li, Chun Schneider, Yannik K.-H. Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
author_facet |
Østnes Hansen, Kine Hansen, Ida Kristine Østnes Ullsten-Wahlund, Sara Jenssen, Marte Isaksson, Johan Mattias Li, Chun Schneider, Yannik K.-H. |
author_sort |
Østnes Hansen, Kine |
title |
Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
title_short |
Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
title_full |
Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
title_fullStr |
Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
title_full_unstemmed |
Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines |
title_sort |
identification of new purpuroine analogues from the arctic echinodermata pteraster militaris that inhibit flt3-itd+ aml cell lines |
publisher |
MDPI |
publishDate |
2022 |
url |
https://hdl.handle.net/10037/28137 https://doi.org/10.3390/ijms232415852 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Arctic |
genre_facet |
Arctic Arctic |
op_relation |
International Journal of Molecular Sciences Østnes Hansen, Hansen, Ullsten-Wahlund, Jenssen, Petit, Isaksson. Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines. International Journal of Molecular Sciences. 2022 FRIDAID 2103455 doi:10.3390/ijms232415852 1661-6596 1422-0067 https://hdl.handle.net/10037/28137 |
op_rights |
Attribution 4.0 International (CC BY 4.0) openAccess Copyright 2022 The Author(s) https://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.3390/ijms232415852 |
container_title |
International Journal of Molecular Sciences |
container_volume |
23 |
container_issue |
24 |
container_start_page |
15852 |
_version_ |
1766298183772667904 |