Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

Marine Drugs

Si-Mei Long³  Feng-Yin Liang³  Qi Wu³  Xi-Lin Lu³  Xiao-Li Yao³  Shi-Chang Li²  Jing Li²  Huanxing Su¹  Ji-Yan Pang² 

[1] State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China; E-Mail:;School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China; E-Mails:;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; E-Mails:

关键词: behavior-based screen;    zebrafish;    PTZ;    c-fos;   

DOI  :  10.3390/md12063307

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.