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Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish
- Source :
- Marine Drugs; Volume 12; Issue 6; Pages: 3307-3322, Marine Drugs, Marine Drugs, Vol 12, Iss 6, Pp 3307-3322 (2014)
- Publication Year :
- 2014
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2014.
-
Abstract
- High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37–42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy.
- Subjects :
- Nervous system
c-fos
Oceans and Seas
Pharmaceutical Science
PTZ
Pharmacology
Motor Activity
Inhibitory postsynaptic potential
c-Fos
Article
behavior-based screen
Epilepsy
Structure-Activity Relationship
Drug Discovery
medicine
Structure–activity relationship
Animals
RNA, Messenger
lcsh:QH301-705.5
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Zebrafish
Pyrans
zebrafish
Messenger RNA
Biological Products
biology
Behavior, Animal
Phenyl Ethers
Fungi
medicine.disease
biology.organism_classification
Small molecule
High-Throughput Screening Assays
Disease Models, Animal
medicine.anatomical_structure
lcsh:Biology (General)
Larva
biology.protein
Pentylenetetrazole
Anticonvulsants
Proto-Oncogene Proteins c-fos
Subjects
Details
- Language :
- English
- ISSN :
- 16603397
- Database :
- OpenAIRE
- Journal :
- Marine Drugs; Volume 12; Issue 6; Pages: 3307-3322
- Accession number :
- edsair.doi.dedup.....58784142f6082ecd9c956a0b8ba8f8b0
- Full Text :
- https://doi.org/10.3390/md12063307