title: Identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish.
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.
authors.affiliation: Department 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, China. longsm@mail.sysu.edu.cn.
authors.forename: Si-Mei
authors.initials: SM
authors.lastname: Long
authors.affiliation: Department 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, China. liangfy@mail2.sysu.edu.cn.
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Liang
authors.affiliation: Department 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, China. wuqi@medmail.com.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department 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, China. goodxilin@163.com.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department 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, China. liliyao71@163.com.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Yao
authors.affiliation: School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. lishich@mail2.sysu.edu.cn.
authors.forename: Shi-Chang
authors.initials: SC
authors.lastname: Li
authors.affiliation: School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. zsulijing@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. Huanxingsu@umac.mo.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.affiliation: School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. cespjy@mail.sysu.edu.cn.
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Pang
authors.affiliation: Department 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, China. peizhong@mail.sysu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D005658:Fungi / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000379:methods; D007814:Larva; D009043:Motor Activity / Q000187:drug effects; D009792:Oceans and Seas; D010433:Pentylenetetrazole; D010647:Phenyl Ethers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011714:Pyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013329:Structure-Activity Relationship; D015027:Zebrafish
chemical_list: D000927:Anticonvulsants; D001688:Biological Products; D010647:Phenyl Ethers; D016760:Proto-Oncogene Proteins c-fos; D011714:Pyrans; D012333:RNA, Messenger; D010433:Pentylenetetrazole