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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ftpubmed:oai:pubmedcentral.nih.gov:9779817 2023-05-15T15:08:51+02:00 Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD(+) AML Cell Lines Ullsten, Sara Petit, Guillaume A. Isaksson, Johan Hansen, Ida K. Ø. Schneider, Yannik K.-H. Jenssen, Marte Li, Chun Hansen, Kine Ø. 2022-12-13 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779817/ https://doi.org/10.3390/ijms232415852 en eng MDPI http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779817/ http://dx.doi.org/10.3390/ijms232415852 © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). CC-BY Int J Mol Sci Article Text 2022 ftpubmed https://doi.org/10.3390/ijms232415852 2022-12-25T02:25:09Z 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. Text Arctic PubMed Central (PMC) Arctic International Journal of Molecular Sciences 23 24 15852 |
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Article Ullsten, Sara Petit, Guillaume A. Isaksson, Johan Hansen, Ida K. Ø. Schneider, Yannik K.-H. Jenssen, Marte Li, Chun Hansen, Kine Ø. Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD(+) AML Cell Lines |
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Article |
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 |
Text |
author |
Ullsten, Sara Petit, Guillaume A. Isaksson, Johan Hansen, Ida K. Ø. Schneider, Yannik K.-H. Jenssen, Marte Li, Chun Hansen, Kine Ø. |
author_facet |
Ullsten, Sara Petit, Guillaume A. Isaksson, Johan Hansen, Ida K. Ø. Schneider, Yannik K.-H. Jenssen, Marte Li, Chun Hansen, Kine Ø. |
author_sort |
Ullsten, Sara |
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 |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779817/ https://doi.org/10.3390/ijms232415852 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
op_source |
Int J Mol Sci |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779817/ http://dx.doi.org/10.3390/ijms232415852 |
op_rights |
© 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
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CC-BY |
op_doi |
https://doi.org/10.3390/ijms232415852 |
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International Journal of Molecular Sciences |
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23 |
container_issue |
24 |
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15852 |
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1766340130939863040 |