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 bif
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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Metadaten
Author:Fengjie Li, Christian Peifer, Dorte Janussen, Deniz Tasdemir
URN:urn:nbn:de:hebis:30:3-533182
DOI:http://dx.doi.org/10.3390/md17080439
ISSN:1660-3397
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=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
Pagenumber: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 
Institutes:Senckenbergische Naturforschende Gesellschaft
Institut für Ökologie, Evolution und Diversität
Dewey Decimal Classification:590 Tiere (Zoologie)
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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