期刊
MARINE DRUGS
卷 17, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/md17080439
关键词
Latrunculia; Antarctica; deep-sea sponge; molecular networking; molecular docking; discorhabdin
资金
- China Scholarship Council
- Deutsche Forschungsgemeinschaft (DFG) [JA 1063/17-1]
- Land Schleswig-Holstein within the funding program Open Access Publikationsfonds
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, [alpha](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 mu M, 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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