Identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish.
Identification of marine neuroactive molecules in behaviour-based screens in the larval zebrafish.
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基于行为的斑马鱼幼体筛选中海洋神经活性分子的鉴定
DOI：
10.3390/md12063307
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发表时间：
2014-05-30
期刊：
影响因子：
5.4
通讯作者：
Pei Z
中科院分区：
文献类型：
--
作者：
Long SM;Liang FY;Wu Q;Lu XL;Yao XL;Li SC;Li J;Su H;Pang JY;Pei Z
斑马鱼高通量行为筛选技术是发现新型神经活性小分子药物治疗癫痫等神经系统疾病的有效途径。为了鉴定神经活性小分子，我们首先从海洋天然产物木缩酮和海洋异戊烯基苯基醚中筛选出36个化合物（1-36），这些化合物是从红树林真菌中得到的。化合物1对斑马鱼幼体的运动活性表现出最有效的抑制作用。进一步合成化合物37-42，然后在斑马鱼的PTZ诱导的癫痫模型中检查其潜在的抗癫痫作用。化合物1和化合物39、40、41能显著抑制PTZ诱导的斑马鱼幼鱼运动亢进和c-fos mRNA的升高。化合物40对PTZ诱导的多动症表现出最有效的抑制作用。构效关系分析表明，12位羟基对木缩酮衍生物的抑菌活性起着关键作用，13位取代基对木缩酮衍生物的抑菌活性具有较好的耐受性。因此，这些衍生物可能为治疗癫痫提供一些新的候选药物。
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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影响因子：
2.9
作者：
Zhdanova, IV;Wang, SY;Danilova, NP
通讯作者：
Danilova, NP
影响因子：
5.3
作者：
Burgess, Harold A.;Granato, Michael
通讯作者：
Granato, Michael
新型海洋真菌天然产物流感病毒神经氨酸酶抑制剂的合成及构效关系（SAR）研究
影响因子：
5.4
作者：
Li, Jing;Zhang, Dingmei;Lin, Yongcheng
通讯作者：
Lin, Yongcheng
DOI：
10.1073/pnas.92.23.10545
发表时间：
1995-11-07
影响因子：
11.1
作者：
BROCKERHOFF, SE;HURLEY, JB;DOWLING, JE
通讯作者：
DOWLING, JE
影响因子：
5.3
作者：
Prober, David A.;Rihel, Jason;Schier, Alexander F.
通讯作者：
Schier, Alexander F.