New Discorhabdin Alkaloids from the Antarctic Deep-Sea Sponge Latrunculia biformis
The sponge genus Latrunculia is a prolific source of discorhabdin type pyrroloiminoquinone alkaloids. In the continuation of our research interest into this genus, we studied the Antarctic deep-sea sponge Latrunculia biformis that showed potent in vitro anticancer activity. A targeted isolation proc...
| Published in: | Marine Drugs |
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| Main Authors: | , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://doi.org/10.3390/md17080439 https://nbn-resolving.org/urn:nbn:de:gbv:8-mods-2020-00105-1 https://macau.uni-kiel.de/receive/macau_mods_00000282 https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00001259/marinedrugs-17-00439-v2(1).pdf |
| Summary: | The sponge genus Latrunculia is a prolific source of discorhabdin type pyrroloiminoquinone alkaloids. In the continuation of our research interest into this genus, we studied the Antarctic deep-sea sponge Latrunculia biformis that showed potent in vitro anticancer activity. A targeted isolation process guided by bioactivity and molecular networking-based metabolomics yielded three known discorhabdins, (-)-discorhabdin L (1), (+)-discorhabdin A (2), (+)-discorhabdin Q (3), and three new discorhabdin analogs (-)-2-bromo-discorhabdin D (4), (-)-1-acetyl-discorhabdin L (5), and (+)-1-octacosatrienoyl-discorhabdin L (6) from the MeOH-soluble portion of the organic extract. The chemical structures of 1-6 were elucidated by extensive NMR, HR-ESIMS, FT-IR, [α]D, and ECD (Electronic Circular Dichroism) spectroscopy analyses. Compounds 1, 5, and 6 showed promising anticancer activity with IC50 values of 0.94, 2.71, and 34.0 µM, respectively. Compounds 1-6 and the enantiomer of 1 ((+)-discorhabdin L, 1e) were docked to the active sites of two anticancer targets, topoisomerase I-II and indoleamine 2,3-dioxygenase (IDO1), to reveal, for the first time, the binding potential of discorhabdins to these proteins. Compounds 5 and 6 are the first discorhabdin analogs with an ester function at C-1 and 6 is the first discorhabdin bearing a long-chain fatty acid at this position. This study confirms Latrunculia sponges to be excellent sources of chemically diverse discorhabdin alkaloids. |
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