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 prod...

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Main Authors:	Si-Mei Long, Feng-Yin Liang, Qi Wu, Xi-Lin Lu, Xiao-Li Yao, Shi-Chang Li, Jing Li, Huanxing Su, Ji-Yan Pang, Zhong Pei
Format:	Article
Language:	English
Published:	MDPI AG 2014-05-01
Series:	Marine Drugs
Subjects:	behavior-based screen zebrafish PTZ c-fos
Online Access:	http://www.mdpi.com/1660-3397/12/6/3307

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spelling	doaj-d024f014921f42a5a69bc1038a31d3042020-11-25T00:52:18ZengMDPI AGMarine Drugs1660-33972014-05-011263307332210.3390/md12063307md12063307Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval ZebrafishSi-Mei Long0Feng-Yin Liang1Qi Wu2Xi-Lin Lu3Xiao-Li Yao4Shi-Chang Li5Jing Li6Huanxing Su7Ji-Yan Pang8Zhong Pei9Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaSchool of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, ChinaSchool of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaHigh-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.http://www.mdpi.com/1660-3397/12/6/3307behavior-based screenzebrafishPTZ c-fos
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Si-Mei Long Feng-Yin Liang Qi Wu Xi-Lin Lu Xiao-Li Yao Shi-Chang Li Jing Li Huanxing Su Ji-Yan Pang Zhong Pei
spellingShingle	Si-Mei Long Feng-Yin Liang Qi Wu Xi-Lin Lu Xiao-Li Yao Shi-Chang Li Jing Li Huanxing Su Ji-Yan Pang Zhong Pei Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish Marine Drugs behavior-based screen zebrafish PTZ c-fos
author_facet	Si-Mei Long Feng-Yin Liang Qi Wu Xi-Lin Lu Xiao-Li Yao Shi-Chang Li Jing Li Huanxing Su Ji-Yan Pang Zhong Pei
author_sort	Si-Mei Long
title	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_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_sort	identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish
publisher	MDPI AG
series	Marine Drugs
issn	1660-3397
publishDate	2014-05-01
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.
topic	behavior-based screen zebrafish PTZ c-fos
url	http://www.mdpi.com/1660-3397/12/6/3307
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Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

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