FN Archimer Export Format PT J TI Cytotoxicity, Fractionation and Dereplication of Extracts of the Dinoflagellate Vulcanodinium rugosum, a Producer of Pinnatoxin G BT AF 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 AS 1:1,2;2:3;3:3;4:3;5:1,2;6:1;7:1,2;8:1;9:1;10:2;11:2;12:1; FF 1:PDG-ODE-LITTORAL-PHYC;2:;3:;4:;5:;6:PDG-ODE-LITTORAL-PHYC;7:;8:PDG-ODE-LITTORAL-PHYC;9:PDG-ODE-LITTORAL-PHYC;10:;11:;12:PDG-ODE-LITTORAL-PHYC; C1 IFREMER, Ctr Atlantique, Lab Phycotoxines, F-44311 Nantes, France. Univ Nantes, LUNAM, Fac Pharm, MMS EA2160, F-44035 Nantes, France. ANSES, Unite Toxicol Contaminants, F-35302 Fougeres, France. C2 IFREMER, FRANCE UNIV NANTES, FRANCE ANSES, FRANCE SI NANTES SE PDG-ODE-LITTORAL-PHYC IN WOS Ifremer jusqu'en 2018 copubli-france copubli-univ-france IF 3.512 TC 11 UR https://archimer.ifremer.fr/doc/00156/26723/24802.pdf LA English DT Article DE ;dereplication;cyclic imine;HRMS;bioactivity;pinnatoxins AB 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. PY 2013 PD SEP SO Marine Drugs SN 1660-3397 PU Mdpi Ag VL 11 IS 9 UT 000328621900016 BP 3350 EP 3371 DI 10.3390/md11093350 ID 26723 ER EF