TY  - JOUR
A1  - Li, Fengjie
A1  - Peifer, Christian
A1  - Janussen, Dorte
A1  - Tasdemir, Deniz
T1  - New discorhabdin alkaloids from the antarctic deep-sea sponge Latrunculia biformis
T2  - Marine drugs
N2  - 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.
KW  - Latrunculia
KW  - Antarctica
KW  - deep-sea sponge
KW  - molecular networking
KW  - molecular docking
KW  - discorhabdin
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53318
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-533182
SN  - 1660-3397
N1  - 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
VL  - 17
IS  - 8, Art. 439
SP  - 1
EP  - 19
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -