PUBLICATION
Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi
- Authors
- Brillatz, T., Lauritano, C., Jacmin, M., Khamma, S., Marcourt, L., Righi, D., Romano, G., Esposito, F., Ianora, A., Queiroz, E.F., Wolfender, J.L., Crawford, A.D.
- ID
- ZDB-PUB-180426-3
- Date
- 2018
- Source
- PLoS One 13: e0196195 (Journal)
- Registered Authors
- Crawford, Alexander
- Keywords
- none
- MeSH Terms
-
- Animals
- Anticonvulsants/chemistry
- Anticonvulsants/isolation & purification
- Anticonvulsants/therapeutic use*
- Chemical Fractionation
- Diatoms/chemistry*
- Disease Models, Animal
- Inosine/chemistry
- Inosine/isolation & purification
- Inosine/therapeutic use*
- Magnetic Resonance Spectroscopy
- Molecular Structure
- Pentylenetetrazole/adverse effects*
- Seizures/chemically induced
- Seizures/drug therapy*
- Zebrafish
- PubMed
- 29689077 Full text @ PLoS One
Citation
Brillatz, T., Lauritano, C., Jacmin, M., Khamma, S., Marcourt, L., Righi, D., Romano, G., Esposito, F., Ianora, A., Queiroz, E.F., Wolfender, J.L., Crawford, A.D. (2018) Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. PLoS One. 13:e0196195.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping