Isolation, structure elucidation, relative lc-ms response, and in vitro toxicity of azaspiracids from the dinoflagellateazadinium spinosum
Wilkins, Alistair L.
Twiner, Michael J.
Miles, Christopher O.
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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
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.