Structure Elucidation, Relative LC–MS Response and In Vitro Toxicity of Azaspiracids 7–10 Isolated from Mussels (Mytilus edulis)

Type Article
Date 2015-05
Language English
Author(s) Kilcoyne Jane1, 2, Twiner Michael J.3, McCarron Pearse4, Crain Sheila4, Giddings Sabrina D.4, Foley Barry2, Rise Frode5, Hess PhilippORCID6, Willdns Alistair L.7, Miles Christopher O.7, 8
Affiliation(s) 1 : Inst Marine, Oranmore, County Galway, Ireland.
2 : Dublin Inst Technol, Sch Chem & Pharmaceut Sci, Dublin 8, Ireland.
3 : Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
4 : Natl Res Council Canada, Measurement Sci & Stand Biotoxin Metrol, Halifax, NS B3H 3Z1, Canada.
5 : Univ Oslo, Dept Chem, N-0315 Oslo, Norway.
6 : Ifremer, Lab Phycotoxines, F-44311 Nantes, France.
7 : Norwegian Vet Inst, N-0106 Oslo, Norway.
8 : Univ Oslo, Sch Pharm, Dept Pharmaceut Chem, N-0316 Oslo, Norway.
Source Journal Of Agricultural And Food Chemistry (0021-8561) (Amer Chemical Soc), 2015-05 , Vol. 63 , N. 20 , P. 5083-5091
DOI 10.1021/acs.jafc.5b01320
WOS© Times Cited 29
Keyword(s) azaspiracid, structure confirmation, LC-MS molar response, NMR, mass spectrometry, purification, Jurkat T, toxicity
Abstract Azaspiracids (AZAs) are marine biotoxins produced by dinoflagellates that can accumulate in shellfish, which if consumed can lead to poisoning events. AZA7–10, 7–10, were isolated from shellfish and their structures, previously proposed on the basis of only LC–MS/MS data, were confirmed by NMR spectroscopy. Purified AZA4–6, 4–6, and 7–10 were accurately quantitated by qNMR and used to assay cytotoxicity with Jurkat T lymphocyte cells for the first time. LC–MS(MS) molar response studies performed using isocratic and gradient elution in both selected ion monitoring and selected reaction monitoring modes showed that responses for the analogues ranged from 0.3 to 1.2 relative to AZA1, 1. All AZA analogues tested were cytotoxic to Jurkat T lymphocyte cells in a time- and concentration-dependent manner; however, there were distinct differences in their EC50 values, with the potencies for each analogue being: AZA6 > AZA8 > AZA1 > AZA4 ≈ AZA9 > AZA5 ≈ AZA10. This data contributes to the understanding of the structure–activity relationships of AZAs.
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Kilcoyne Jane, Twiner Michael J., McCarron Pearse, Crain Sheila, Giddings Sabrina D., Foley Barry, Rise Frode, Hess Philipp, Willdns Alistair L., Miles Christopher O. (2015). Structure Elucidation, Relative LC–MS Response and In Vitro Toxicity of Azaspiracids 7–10 Isolated from Mussels (Mytilus edulis). Journal Of Agricultural And Food Chemistry, 63(20), 5083-5091. Publisher's official version : , Open Access version :