New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889)
<i>Thorectandra choanoides</i> (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Ch...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/2/97 |
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| author | Shamsunnahar Khushi Angela A. Salim Ahmed H. Elbanna Laizuman Nahar Robert J. Capon |
| author_facet | Shamsunnahar Khushi Angela A. Salim Ahmed H. Elbanna Laizuman Nahar Robert J. Capon |
| author_sort | Shamsunnahar Khushi |
| collection | DOAJ |
| description | <i>Thorectandra choanoides</i> (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (<b>1</b>), with the GNPS cluster revealing a halo of related alkaloids <b>1a</b>–<b>1n</b>. In considering biosynthetic origins, we propose that <i>Thorectandra</i><i>choanoides</i> (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (<b>2</b>), 6-bromoaplysinopsin (<b>3</b>), aplysinopsin (<b>4</b>), and 1′,8-dihydroaplysinopsin (<b>10</b>), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-<i>like</i> (IDO) enzyme to <b>1a</b>–<b>1n</b>. Where the 1′,8-dihydroalkaloids <b>2</b> and <b>10</b> are fully transformed to stable ring-opened thorectandrins <b>1</b> and <b>1a</b>–<b>1b</b>, and <b>1h</b>–<b>1j</b>, respectively, the conjugated precursors <b>3</b> and <b>4</b> are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts <b>1c</b>–<b>1g</b>, and <b>1k</b>–<b>1n</b>, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme. |
| first_indexed | 2024-03-09T05:04:11Z |
| format | Article |
| id | doaj.art-8a28006de74a4cc28ee4ed49a7fcbe41 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T05:04:11Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-8a28006de74a4cc28ee4ed49a7fcbe412023-12-03T12:57:16ZengMDPI AGMarine Drugs1660-33972021-02-011929710.3390/md19020097New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889)Shamsunnahar Khushi0Angela A. Salim1Ahmed H. Elbanna2Laizuman Nahar3Robert J. Capon4Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia<i>Thorectandra choanoides</i> (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (<b>1</b>), with the GNPS cluster revealing a halo of related alkaloids <b>1a</b>–<b>1n</b>. In considering biosynthetic origins, we propose that <i>Thorectandra</i><i>choanoides</i> (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (<b>2</b>), 6-bromoaplysinopsin (<b>3</b>), aplysinopsin (<b>4</b>), and 1′,8-dihydroaplysinopsin (<b>10</b>), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-<i>like</i> (IDO) enzyme to <b>1a</b>–<b>1n</b>. Where the 1′,8-dihydroalkaloids <b>2</b> and <b>10</b> are fully transformed to stable ring-opened thorectandrins <b>1</b> and <b>1a</b>–<b>1b</b>, and <b>1h</b>–<b>1j</b>, respectively, the conjugated precursors <b>3</b> and <b>4</b> are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts <b>1c</b>–<b>1g</b>, and <b>1k</b>–<b>1n</b>, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.https://www.mdpi.com/1660-3397/19/2/97<i>Thorectandra choanoides</i>tryptophan alkaloidindoleamine 2,3-dioxygenaseaplysinopsinsGNPS molecular network |
| spellingShingle | Shamsunnahar Khushi Angela A. Salim Ahmed H. Elbanna Laizuman Nahar Robert J. Capon New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) Marine Drugs <i>Thorectandra choanoides</i> tryptophan alkaloid indoleamine 2,3-dioxygenase aplysinopsins GNPS molecular network |
| title | New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) |
| title_full | New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) |
| title_fullStr | New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) |
| title_full_unstemmed | New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) |
| title_short | New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, <i>Thorectandra choanoides</i> (CMB-01889) |
| title_sort | new from old thorectandrin alkaloids in a southern australian marine sponge i thorectandra choanoides i cmb 01889 |
| topic | <i>Thorectandra choanoides</i> tryptophan alkaloid indoleamine 2,3-dioxygenase aplysinopsins GNPS molecular network |
| url | https://www.mdpi.com/1660-3397/19/2/97 |
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