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Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish
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 produ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071578/ https://www.ncbi.nlm.nih.gov/pubmed/24886868 http://dx.doi.org/10.3390/md12063307 |
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author | Long, Si-Mei Liang, Feng-Yin Wu, Qi Lu, Xi-Lin Yao, Xiao-Li Li, Shi-Chang Li, Jing Su, Huanxing Pang, Ji-Yan Pei, Zhong |
author_facet | Long, Si-Mei Liang, Feng-Yin Wu, Qi Lu, Xi-Lin Yao, Xiao-Li Li, Shi-Chang Li, Jing Su, Huanxing Pang, Ji-Yan Pei, Zhong |
author_sort | Long, Si-Mei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4071578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-40715782014-06-26 Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish Long, Si-Mei Liang, Feng-Yin Wu, Qi Lu, Xi-Lin Yao, Xiao-Li Li, Shi-Chang Li, Jing Su, Huanxing Pang, Ji-Yan Pei, Zhong Mar Drugs Article 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. MDPI 2014-05-30 /pmc/articles/PMC4071578/ /pubmed/24886868 http://dx.doi.org/10.3390/md12063307 Text en © 2014 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/). |
spellingShingle | Article Long, Si-Mei Liang, Feng-Yin Wu, Qi Lu, Xi-Lin Yao, Xiao-Li Li, Shi-Chang Li, Jing Su, Huanxing Pang, Ji-Yan Pei, Zhong Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title | Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title_full | Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title_fullStr | Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title_full_unstemmed | Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title_short | Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish |
title_sort | identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071578/ https://www.ncbi.nlm.nih.gov/pubmed/24886868 http://dx.doi.org/10.3390/md12063307 |
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