Identification of 21,22-Dehydroazaspiracids in Mussels (Mytilus edulis) and in Vitro Toxicity of Azaspiracid-26

Azaspiracids (AZAs) are marine biotoxins produced by the genera Azadinium and Amphidoma, pelagic marine dinoflagellates that may accumulate in shellfish resulting in human illness following consumption. The complexity of these toxins has been well documented, with more than 40 structural variants reported that are produced by dinoflagellates, result from metabolism in shellfish, or are extraction artifacts. Approximately 34 μg of a new AZA with MW 823 Da (AZA26 (3)) was isolated from blue mussels (Mytilus edulis), and its structure determined by MS and NMR spectroscopy. AZA26, possibly a bioconversion product of AZA5, lacked the C-20–C-21 diol present in all AZAs reported thus far and had a 21,22-olefin and a keto group at C-23. Toxicological assessment of 3 using an in vitro model system based on Jurkat T lymphocyte cells showed the potency to be ∼30-fold lower than that of AZA1. The corresponding 21,22-dehydro-23-oxo-analogue of AZA10 (AZA28) and 21,22-dehydro analogues of AZA3, -4, -5, -6, -9, and -10 (AZA25, -48 (4), -60, -27, -49, and -61, respectively) were also identified by HRMS/MS, periodate cleavage reactivity, conversion from known analogues, and NMR (for 4 that was present in a partially purified sample of AZA7).

URI

http://hdl.handle.net/10793/1822

Description

Peer reviewed The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.7b00973. J. Nat. Prod. 2018, 81, 4, 885–893 Publication Date:February 28, 2018 https://doi.org/10.1021/acs.jnatprod.7b00973 Copyright © 2018 American Chemical Society and American Society of Pharmacognosy

Citation

Kilcoyne, J., McCarron, P., Twiner, M. J., Rise, F., Hess, P., Wilkins, A. L., & Miles, C. O. (2018). Identification of 21, 22-dehydroazaspiracids in mussels (Mytilus edulis) and in vitro toxicity of azaspiracid-26. Journal of natural products, 81(4), 885-893. https://doi.org/10.1021/acs.jnatprod.7b00973