Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite
From the CH(2)Cl(2) extract of the Antarctic sponge Dendrilla antarctica we found spongian diterpenes, including previously reported aplysulphurin (1), tetrahydroaplysulphurin-1 (2), membranolide (3), and darwinolide (4), utilizing a CH(2)Cl(2)/MeOH extraction scheme. However, the extracts also yiel...
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ftpubmed:oai:pubmedcentral.nih.gov:8351534 2023-05-15T13:36:34+02:00 Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite Shilling, Andrew J. Witowski, Christopher G. Maschek, J. Alan Azhari, Ala Vesely, Brian A. Kyle, Dennis E. Amsler, Charles D. McClintock, James B. Baker, Bill J. 2020-04-13 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351534/ http://www.ncbi.nlm.nih.gov/pubmed/32281798 https://doi.org/10.1021/acs.jnatprod.0c00025 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351534/ http://www.ncbi.nlm.nih.gov/pubmed/32281798 http://dx.doi.org/10.1021/acs.jnatprod.0c00025 J Nat Prod Article Text 2020 ftpubmed https://doi.org/10.1021/acs.jnatprod.0c00025 2021-08-15T00:45:37Z From the CH(2)Cl(2) extract of the Antarctic sponge Dendrilla antarctica we found spongian diterpenes, including previously reported aplysulphurin (1), tetrahydroaplysulphurin-1 (2), membranolide (3), and darwinolide (4), utilizing a CH(2)Cl(2)/MeOH extraction scheme. However, the extracts also yielded diterpenes bearing one or more methyl acetal functionalities (5–9), two of which are previously unreported, while others are revised here. Further investigation of diterpene reactivity led to additional new metabolites (10–12), which identified them as well as the methyl acetals as artifacts from methanolysis of aplysulphurin. The bioactivity of the methanolysis products, membranoids A–H (5–12), as well as natural products 1–4, were assessed for activity against Leishmania donovani-infected J774A.1 macrophages, revealing insights into their structure/activity relationships. Four diterpenes, tetrahydroaplysulphurin-1 (2) as well as membranoids B (6), D (8), and G (11), displayed low micromolar activity against L. donovani with no discernible cytotoxicity against uninfected J774A.1 cells. Leishmaniasis is a neglected tropical disease that affects one million people every year and can be fatal if left untreated. Text Antarc* Antarctic Antarctica PubMed Central (PMC) Antarctic The Antarctic Journal of Natural Products 83 5 1553 1562 |
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Article Shilling, Andrew J. Witowski, Christopher G. Maschek, J. Alan Azhari, Ala Vesely, Brian A. Kyle, Dennis E. Amsler, Charles D. McClintock, James B. Baker, Bill J. Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
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description |
From the CH(2)Cl(2) extract of the Antarctic sponge Dendrilla antarctica we found spongian diterpenes, including previously reported aplysulphurin (1), tetrahydroaplysulphurin-1 (2), membranolide (3), and darwinolide (4), utilizing a CH(2)Cl(2)/MeOH extraction scheme. However, the extracts also yielded diterpenes bearing one or more methyl acetal functionalities (5–9), two of which are previously unreported, while others are revised here. Further investigation of diterpene reactivity led to additional new metabolites (10–12), which identified them as well as the methyl acetals as artifacts from methanolysis of aplysulphurin. The bioactivity of the methanolysis products, membranoids A–H (5–12), as well as natural products 1–4, were assessed for activity against Leishmania donovani-infected J774A.1 macrophages, revealing insights into their structure/activity relationships. Four diterpenes, tetrahydroaplysulphurin-1 (2) as well as membranoids B (6), D (8), and G (11), displayed low micromolar activity against L. donovani with no discernible cytotoxicity against uninfected J774A.1 cells. Leishmaniasis is a neglected tropical disease that affects one million people every year and can be fatal if left untreated. |
format |
Text |
author |
Shilling, Andrew J. Witowski, Christopher G. Maschek, J. Alan Azhari, Ala Vesely, Brian A. Kyle, Dennis E. Amsler, Charles D. McClintock, James B. Baker, Bill J. |
author_facet |
Shilling, Andrew J. Witowski, Christopher G. Maschek, J. Alan Azhari, Ala Vesely, Brian A. Kyle, Dennis E. Amsler, Charles D. McClintock, James B. Baker, Bill J. |
author_sort |
Shilling, Andrew J. |
title |
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
title_short |
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
title_full |
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
title_fullStr |
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
title_full_unstemmed |
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite |
title_sort |
spongian diterpenoids derived from the antarctic sponge dendrilla antarctica are potent inhibitors of the leishmania parasite |
publishDate |
2020 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351534/ http://www.ncbi.nlm.nih.gov/pubmed/32281798 https://doi.org/10.1021/acs.jnatprod.0c00025 |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic Antarctica |
genre_facet |
Antarc* Antarctic Antarctica |
op_source |
J Nat Prod |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351534/ http://www.ncbi.nlm.nih.gov/pubmed/32281798 http://dx.doi.org/10.1021/acs.jnatprod.0c00025 |
op_doi |
https://doi.org/10.1021/acs.jnatprod.0c00025 |
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Journal of Natural Products |
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83 |
container_issue |
5 |
container_start_page |
1553 |
op_container_end_page |
1562 |
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1766080708605902848 |