Isolation, Structure Elucidation, Relative LC-MS Response, and in Vitro Toxicity of Azaspiracids from the Dinoflagellate Azadinium spinosum

Type Article
Date 2014-11
Language English
Author(s) Kilcoyne Jane1, 2, Nulty Ciara1, Jauffrais ThierryORCID3, 4, McCarron Pearse5, Herve FabienneORCID3, Foley Barry2, Rise Frode6, Crain Sheila5, Wilkins Alistair L.7, Twiner Michael J.8, Hess PhilippORCID3, Miles Christopher O.7, 9
Affiliation(s) 1 : Inst Marine, Galway, Ireland.
2 : Dublin Inst Technol, Sch Chem & Pharmaceut Sci, Dublin 8, Ireland.
3 : IFREMER, Lab Phycotoxines, F-44311 Nantes, France.
4 : Univ Nantes, Fac Sci & Tech, Mer Mol Sante EA2160, F-44322 Nantes, France.
5 : Natl Res Council Canada, Halifax, NS B3H 3Z1, Canada.
6 : Univ Oslo, Dept Chem, N-0315 Oslo, Norway.
7 : Norwegian Vet Inst, N-0106 Oslo, Norway.
8 : Univ Michigan, Dept Nat Sci, Dearborn, MI 48128 USA.
9 : Univ Oslo, Sch Pharm, Dept Pharmaceut Chem, N-0316 Oslo, Norway.
Source Journal Of Natural Products (0163-3864) (Amer Chemical Soc), 2014-11 , Vol. 77 , N. 11 , P. 2465-2474
DOI 10.1021/np500555k
WOS© Times Cited 24
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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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 Dinoflagellate Azadinium spinosum. Journal Of Natural Products, 77(11), 2465-2474. Publisher's official version : https://doi.org/10.1021/np500555k , Open Access version : https://archimer.ifremer.fr/doc/00245/35606/