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Isolation, structure elucidation, relative lc-ms response, and in vitro toxicity of azaspiracids from the dinoflagellateazadinium spinosum

Kilcoyne, Jane
; 
Nulty, Ciara
; 
Jauffrais, Thierry
; 
McCarron, Pearse
; 
Herve, Fabienne
; 
Foley, Barry
; 
Rise, Frode
; 
Crain, Sheila
; 
Wilkins, Alistair L.
; 
Twiner, Michael J.
... show 2 more
Identifiers
http://hdl.handle.net/10379/12266
https://doi.org/10.13025/27336
Repository DOI
10.1021/np500555k
Publication Date
2014-11-26
Keywords
mussels mytilus-edulis, sp-nov, calibration solutions, algal toxins, marine toxin, cell-lines, shellfish, dinophyceae, analogs, sea
Type
Article
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Citation
Kilcoyne, Jane; Nulty, Ciara; Jauffrais, Thierry; McCarron, Pearse; Herve, Fabienne; Foley, Barry; Rise, Frode; Crain, Sheila; Wilkins, Alistair L. Twiner, Michael J.; Hess, Philipp; Miles, Christopher O. (2014). Isolation, structure elucidation, relative lc-ms response, and in vitro toxicity of azaspiracids from the dinoflagellateazadinium spinosum. Journal of Natural Products 77 (11), 2465-2474
Abstract
We identified three new azaspiracids (AZAs) with molecular weights of 715, 815, and 829 (AZA33 (3), AZA34 (4), and AZA35, respectively) in mussels, seawater, and Azadinium spinosum culture. Approximately 700 mu g of 3 and 250 mu g of 4 were isolated from a bulk culture of A. spinosum, and their structures determined by MS and NMR spectroscopy. These compounds differ significantly at the carboxyl end of the molecule from known AZA analogues and therefore provide valuable information on structure-activity relationships. Initial toxicological assessment was performed using an in vitro model system based on Jurkat T lymphocyte cytotoxicity, and the potencies of 3 and 4 were found to be 0.22- and 5.5-fold that of AZA1 (1), respectively. Thus, major changes in the carboxyl end of 1 resulted in significant changes in toxicity. In mussel extracts, 3 was detected at low levels, whereas 4 and AZA35 were detected only at extremely low levels or not at all. The structures of 3 and 4 are consistent with AZAs being biosynthetically assembled from the amino end.
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Publisher
American Chemical Society (ACS)
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)