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Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi.
Brillatz, Théo; Lauritano, Chiara; Jacmin, Maxime; Khamma, Supitcha; Marcourt, Laurence; Righi, Davide; Romano, Giovanna; Esposito, Francesco; Ianora, Adrianna; Queiroz, Emerson F; Wolfender, Jean-Luc; Crawford, Alexander D.
Afiliação
  • Brillatz T; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
  • Lauritano C; Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
  • Jacmin M; Luxembourg Centre for Systems Biomedicine, Université du Luxembourg, Belvaux, Luxembourg.
  • Khamma S; Theracule S.á r.l., Belval, Luxembourg.
  • Marcourt L; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
  • Righi D; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
  • Romano G; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
  • Esposito F; Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
  • Ianora A; Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
  • Queiroz EF; Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
  • Wolfender JL; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
  • Crawford AD; School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
PLoS One ; 13(4): e0196195, 2018.
Article em En | MEDLINE | ID: mdl-29689077
With the goal of identifying neuroactive secondary metabolites from microalgae, a microscale in vivo zebrafish bioassay for antiseizure activity was used to evaluate bioactivities of the diatom Skeletonema marinoi, which was recently revealed as being a promising source of drug-like small molecules. A freeze-dried culture of S. marinoi was extracted by solvents with increasing polarities (hexane, dichloromethane, methanol and water) and these extracts were screened for anticonvulsant activity using a larval zebrafish epilepsy model with seizures induced by the GABAA antagonist pentylenetetrazole. The methanolic extract of S. marinoi exhibited significant anticonvulsant activity and was chosen for bioassay-guided fractionation, which associated the bioactivity with minor constituents. The key anticonvulsant constituent was identified as the nucleoside inosine, a well-known adenosine receptor agonist with previously reported antiseizure activities in mice and rat epilepsy models, but not reported to date as a bioactive constituent of microalgae. In addition, a UHPLC-HRMS metabolite profiling was used for dereplication of the other constituents of S. marinoi. Structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution spectrometry. These results highlight the potential of zebrafish-based screening and bioassay-guided fractionation to identify neuroactive marine natural products.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Pentilenotetrazol / Convulsões / Diatomáceas / Inosina / Anticonvulsivantes Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Pentilenotetrazol / Convulsões / Diatomáceas / Inosina / Anticonvulsivantes Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça