Novel N-methylated 8-oxoisoguanines from Pacific sponges with diverse neuroactivities.
Novel N-methylated 8-oxoisoguanines from Pacific sponges with diverse neuroactivities.
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DOI：
10.1021/jm100490m
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发表时间：
2010-08-26
影响因子：
7.3
通讯作者：
Sakai R
中科院分区：
文献类型：
--
作者：
Sakurada T;Gill MB;Frausto S;Copits B;Noguchi K;Shimamoto K;Swanson GT;Sakai R
海洋生物产生了各种具有神经药理学应用的代谢物。在这里，我们描述了四个新的，神经活性嘌呤1-4，从收集在帕劳共和国的Haplosclerida海绵分离和药理学特性。通过光谱和X射线衍射数据分析确定了结构。化合物1在脑室内注射到小鼠中时诱导惊厥，其中CD 50值为2.4nmol/小鼠。嘌呤2-4在较高剂量下在小鼠生物测定中具有活性。在海马神经元的电生理记录中，1的神经元生成活性与神经元GABA能传递的抑制相关，仅对兴奋性信号传导有适度影响。尽管具有嘌呤模板结构，1的抑制活性不被非选择性腺苷受体拮抗剂阻止。因此，1代表一种新的取代嘌呤，通过其对抑制性神经传递的作用来诱发惊厥。这些8-氧代异鸟嘌呤类似物包括在结构上与内源性神经信号分子和常用CNS兴奋剂密切相关的新化合物家族。
Marine organisms have yielded a variety of metabolites with neuropharmacological applications. Here we describe the isolation and pharmacological characterization of four novel, neurologically active purines 1–4, isolated from Haplosclerida sponges collected in the Republic of Palau. The structures were determined by analyses of spectral and X-ray data. Compound 1 induced convulsions upon intracerebroventricular injection into mice, with a CD50 value of 2.4 nmol/mouse. Purines 2–4 were active in mouse bioassays at higher doses. The seizurogenic activity of 1 was correlated with inhibition of neuronal GABAergic transmission, with only a modest impact on excitatory signaling, in electrophysiological recordings from hippocampal neurons. Despite having a purine template structure, the inhibitory activity of 1 was not prevented by a nonselective adenosine receptor antagonist. Thus, 1 represents a novel substituted purine that elicits convulsions through its actions on inhibitory neurotransmission. These 8-oxoisoguanine analogs comprise a new family of compounds closely related in structure to endogenous neurosignaling molecules and commonly used CNS stimulants.
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影响因子：
4.7
作者：
De Koninck, Y;Mody, I
通讯作者：
Mody, I
影响因子：
5
作者：
SILLS, MA;FAGG, G;WILLIAMS, M
通讯作者：
WILLIAMS, M
影响因子：
1.7
作者：
Sugimoto, T;Sugimoto, M;Okada, S
通讯作者：
Okada, S
影响因子：
5.3
作者：
DRAGUNOW, M;GODDARD, GV
通讯作者：
GODDARD, GV
DOI：
10.1039/p19860002051
发表时间：
1986-12-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
ZELNIK, R;HARAGUCHI, M;WEIS, AL
通讯作者：
WEIS, AL