Marine Drugs
(Jun 2021)
Agelasine Diterpenoids and Cbl-b Inhibitory Ageliferins from the Coralline Demosponge <em>Astrosclera willeyana</em>
Wei Jiang,
Dongdong Wang,
Brice A. P. Wilson,
Unwoo Kang,
Heidi R. Bokesch,
Emily A. Smith,
Antony Wamiru,
Ekaterina I. Goncharova,
Donna Voeller,
Stanley Lipkowitz,
Barry R. O’Keefe,
Kirk R. Gustafson
Affiliations
Wei Jiang
Marine Science & Technology Institute, College of Environmental Science & Engineering, Yangzhou University, Yangzhou 225127, China
Dongdong Wang
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Brice A. P. Wilson
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Unwoo Kang
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Heidi R. Bokesch
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Emily A. Smith
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Antony Wamiru
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Ekaterina I. Goncharova
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Donna Voeller
Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA
Stanley Lipkowitz
Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA
Barry R. O’Keefe
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
Kirk R. Gustafson
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA
DOI
https://doi.org/10.3390/md19070361
Journal volume & issue
Vol. 19,
no. 7
Abstract
Read online
An extract of the coralline demosponge Astrosclera willeyana inhibited the ubiquitin ligase activity of the immunomodulatory protein Cbl-b. The bioassay-guided separation of the extract provided ten active compounds, including three new N-methyladenine-containing diterpenoids, agelasines W–Y (1–3), a new bromopyrrole alkaloid, N(1)-methylisoageliferin (4), and six known ageliferin derivatives (5–10). The structures of the new compounds were elucidated from their spectroscopic and spectrometric data, including IR, HRESIMS, and NMR, and by comparison with spectroscopic data in the literature. While all of the isolated compounds showed Cbl-b inhibitory activities, ageliferins (4–10) were the most potent metabolites, with IC50 values that ranged from 18 to 35 μM.
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