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Provedor de dados:  5
País:  France
Título:  Cytotoxicity, Fractionation and Dereplication of Extracts of the Dinoflagellate Vulcanodinium rugosum, a Producer of Pinnatoxin G
Autores:  Geiger, Marie
Desanglois, Gwenaelle
Hogeveen, Kevin
Fessard, Valerie
Lepretre, Thomas
Mondeguer, Florence
Guitton, Yann
Herve, Fabienne
Sechet, Veronique
Grovel, Olivier
Pouchus, Yves-francois
Hess, Philipp
Data:  2013-09
Ano:  2013
Palavras-chave:  Dereplication
Cyclic imine
HRMS
Bioactivity
Pinnatoxins
Resumo:  Pinnatoxin G (PnTX-G) is a marine toxin belonging to the class of cyclic imines and produced by the dinoflagellate Vulcanodinium rugosum. In spite of its strong toxicity to mice, leading to the classification of pinnatoxins into the class of “fast-acting toxins”, its hazard for human health has never been demonstrated. In this study, crude extracts of V. rugosum exhibited significant cytotoxicity against Neuro2A and KB cells. IC50 values of 0.38 µg mL−1 and 0.19 µg mL−1 were estimated on Neuro2A cells after only 24 h of incubation and on KB cells after 72 h of incubation, respectively. In the case of Caco-2 cells 48 h after exposure, the crude extract of V. rugosum induced cell cycle arrest accompanied by a dramatic increase in double strand DNA breaks, although only 40% cytotoxicity was observed at the highest concentration tested (5 µg mL−1). However, PnTX-G was not a potent cytotoxic compound as no reduction of the cell viability was observed on the different cell lines. Moreover, no effects on the cell cycle or DNA damage were observed following treatment of undifferentiated Caco-2 cells with PnTX-G. The crude extract of V. rugosum was thus partially purified using liquid-liquid partitioning and SPE clean-up. In vitro assays revealed strong activity of some fractions containing no PnTX-G. The crude extract and the most potent fraction were evaluated using full scan and tandem high resolution mass spectrometry. The dereplication revealed the presence of a major compound that could be putatively annotated as nakijiquinone A, N-carboxy-methyl-smenospongine or stachybotrin A, using the MarinLit™ database. Further investigations will be necessary to confirm the identity of the compounds responsible for the cytotoxicity and genotoxicity of the extracts of V. rugosum.
Tipo:  Text
Idioma:  Inglês
Identificador:  http://archimer.ifremer.fr/doc/00156/26723/24802.pdf

DOI:10.3390/md11093350
Editor:  Mdpi Ag
Relação:  http://archimer.ifremer.fr/doc/00156/26723/
Formato:  application/pdf
Fonte:  Marine Drugs (1660-3397) (Mdpi Ag), 2013-09 , Vol. 11 , N. 9 , P. 3350-3371
Direitos:  2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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