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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
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.
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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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