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 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.
Author: | Fengjie LiORCiDGND, Christian PeiferORCiDGND, Dorte Janussen, Deniz TasdemirORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-533182 |
DOI: | https://doi.org/10.3390/md17080439 |
ISSN: | 1660-3397 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31349703 |
Parent Title (English): | Marine drugs |
Publisher: | Molecular Diversity Preservation International |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Year of Completion: | 2019 |
Date of first Publication: | 2019/07/25 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/03/23 |
Tag: | Antarctica; Latrunculia; deep-sea sponge; discorhabdin; molecular docking; molecular networking |
Volume: | 17 |
Issue: | 8, Art. 439 |
Page Number: | 19 |
First Page: | 1 |
Last Page: | 19 |
Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
HeBIS-PPN: | 464891256 |
Institutes: | Angeschlossene und kooperierende Institutionen / Senckenbergische Naturforschende Gesellschaft |
Biowissenschaften / Institut für Ökologie, Evolution und Diversität | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 59 Tiere (Zoologie) / 590 Tiere (Zoologie) |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |